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Gene Information
Gene symbol: PDCD1
Gene name: programmed cell death 1
HGNC ID: 8760
Synonyms: CD279, PD1
Related Genes
Related Sentences
| # | PMID | Sentence |
| 1 | 11283156 | B7-DC fails to bind the B7.1/2 receptors CD28 and cytotoxic T lymphocyte-associated antigen (CTLA)-4, but does bind PD-1, a receptor for B7-H1/PD-L1. |
| 2 | 11283156 | In particular, B7-DC strongly costimulates interferon gamma but not interleukin (IL)-4 or IL-10 production from isolated naive T cells. |
| 3 | 16382236 | Here we report that PD-1 (programmed death 1; also known as Pdcd1) was selectively upregulated by the exhausted T cells, and that in vivo administration of antibodies that blocked the interaction of this inhibitory receptor with its ligand, PD-L1 (also known as B7-H1), enhanced T-cell responses. |
| 4 | 16382236 | Notably, we found that even in persistently infected mice that were lacking CD4 T-cell help, blockade of the PD-1/PD-L1 inhibitory pathway had a beneficial effect on the 'helpless' CD8 T cells, restoring their ability to undergo proliferation, secrete cytokines, kill infected cells and decrease viral load. |
| 5 | 16382236 | Here we report that PD-1 (programmed death 1; also known as Pdcd1) was selectively upregulated by the exhausted T cells, and that in vivo administration of antibodies that blocked the interaction of this inhibitory receptor with its ligand, PD-L1 (also known as B7-H1), enhanced T-cell responses. |
| 6 | 16382236 | Notably, we found that even in persistently infected mice that were lacking CD4 T-cell help, blockade of the PD-1/PD-L1 inhibitory pathway had a beneficial effect on the 'helpless' CD8 T cells, restoring their ability to undergo proliferation, secrete cytokines, kill infected cells and decrease viral load. |
| 7 | 16409137 | Checkpoints being targeted include CTLA-4 and PD1 that are negative signaling receptors expressed on activated T cells, CD4+CD25+ Foxp3-expressing Tregs (suppressor T cells), IL-2-mediated activation-induced cell death (AICD), and the cytokine TGFbeta. |
| 8 | 16931603 | Molecular adjuvants can be considered in the following groups: TNF superfamily molecules such as CD40 ligand; agonists for TLRs; agonists for NAIP, CIITA, HET-E, TP-1-leucine-rich repeat pathway receptors, such as nucleotide-binding and oligomerization domain (NOD)1, NOD2, and cryopyrin; chemokines; ILs; CSFs; IFNs; alarmins; and purinergic P2X7 receptor agonists. |
| 9 | 16931603 | Complementing these positively acting agents are strategies to reduce the immunosuppressive effects of CD4+CD25+ regulatory T cells and negatively acting factors such as TGF-beta, IL-10, suppressor of cytokine signaling 1, and programmed cell death-1 using neutralizing antibodies, antisense, and small interfering RNA. |
| 10 | 16954372 | PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection. |
| 11 | 16954372 | Here, we report on the expression of programmed death (PD)-1 on human virus-specific CD8(+) T cells and the effect of manipulating signaling through PD-1 on the survival, proliferation, and cytokine function of these cells. |
| 12 | 16954372 | PD-1 expression was found to be low on naive CD8(+) T cells and increased on memory CD8(+) T cells according to antigen specificity. |
| 13 | 16954372 | Memory CD8(+) T cells specific for poorly controlled chronic persistent virus (HIV) more frequently expressed PD-1 than memory CD8(+) T cells specific for well-controlled persistent virus (cytomegalovirus) or acute (vaccinia) viruses. |
| 14 | 16954372 | PD-1 expression was independent of maturational markers on memory CD8(+) T cells and was not directly associated with an inability to produce cytokines. |
| 15 | 16954372 | Importantly, the level of PD-1 surface expression was the primary determinant of apoptosis sensitivity of virus-specific CD8(+) T cells. |
| 16 | 16954372 | Therefore, PD-1 is a major regulator of apoptosis that can impact the frequency of antiviral T cells in chronic infections such as HIV, and could be manipulated to improve HIV-specific CD8(+) T cell numbers, but possibly not all functions in vivo. |
| 17 | 16954372 | PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection. |
| 18 | 16954372 | Here, we report on the expression of programmed death (PD)-1 on human virus-specific CD8(+) T cells and the effect of manipulating signaling through PD-1 on the survival, proliferation, and cytokine function of these cells. |
| 19 | 16954372 | PD-1 expression was found to be low on naive CD8(+) T cells and increased on memory CD8(+) T cells according to antigen specificity. |
| 20 | 16954372 | Memory CD8(+) T cells specific for poorly controlled chronic persistent virus (HIV) more frequently expressed PD-1 than memory CD8(+) T cells specific for well-controlled persistent virus (cytomegalovirus) or acute (vaccinia) viruses. |
| 21 | 16954372 | PD-1 expression was independent of maturational markers on memory CD8(+) T cells and was not directly associated with an inability to produce cytokines. |
| 22 | 16954372 | Importantly, the level of PD-1 surface expression was the primary determinant of apoptosis sensitivity of virus-specific CD8(+) T cells. |
| 23 | 16954372 | Therefore, PD-1 is a major regulator of apoptosis that can impact the frequency of antiviral T cells in chronic infections such as HIV, and could be manipulated to improve HIV-specific CD8(+) T cell numbers, but possibly not all functions in vivo. |
| 24 | 16954372 | PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection. |
| 25 | 16954372 | Here, we report on the expression of programmed death (PD)-1 on human virus-specific CD8(+) T cells and the effect of manipulating signaling through PD-1 on the survival, proliferation, and cytokine function of these cells. |
| 26 | 16954372 | PD-1 expression was found to be low on naive CD8(+) T cells and increased on memory CD8(+) T cells according to antigen specificity. |
| 27 | 16954372 | Memory CD8(+) T cells specific for poorly controlled chronic persistent virus (HIV) more frequently expressed PD-1 than memory CD8(+) T cells specific for well-controlled persistent virus (cytomegalovirus) or acute (vaccinia) viruses. |
| 28 | 16954372 | PD-1 expression was independent of maturational markers on memory CD8(+) T cells and was not directly associated with an inability to produce cytokines. |
| 29 | 16954372 | Importantly, the level of PD-1 surface expression was the primary determinant of apoptosis sensitivity of virus-specific CD8(+) T cells. |
| 30 | 16954372 | Therefore, PD-1 is a major regulator of apoptosis that can impact the frequency of antiviral T cells in chronic infections such as HIV, and could be manipulated to improve HIV-specific CD8(+) T cell numbers, but possibly not all functions in vivo. |
| 31 | 16954372 | PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection. |
| 32 | 16954372 | Here, we report on the expression of programmed death (PD)-1 on human virus-specific CD8(+) T cells and the effect of manipulating signaling through PD-1 on the survival, proliferation, and cytokine function of these cells. |
| 33 | 16954372 | PD-1 expression was found to be low on naive CD8(+) T cells and increased on memory CD8(+) T cells according to antigen specificity. |
| 34 | 16954372 | Memory CD8(+) T cells specific for poorly controlled chronic persistent virus (HIV) more frequently expressed PD-1 than memory CD8(+) T cells specific for well-controlled persistent virus (cytomegalovirus) or acute (vaccinia) viruses. |
| 35 | 16954372 | PD-1 expression was independent of maturational markers on memory CD8(+) T cells and was not directly associated with an inability to produce cytokines. |
| 36 | 16954372 | Importantly, the level of PD-1 surface expression was the primary determinant of apoptosis sensitivity of virus-specific CD8(+) T cells. |
| 37 | 16954372 | Therefore, PD-1 is a major regulator of apoptosis that can impact the frequency of antiviral T cells in chronic infections such as HIV, and could be manipulated to improve HIV-specific CD8(+) T cell numbers, but possibly not all functions in vivo. |
| 38 | 16954372 | PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection. |
| 39 | 16954372 | Here, we report on the expression of programmed death (PD)-1 on human virus-specific CD8(+) T cells and the effect of manipulating signaling through PD-1 on the survival, proliferation, and cytokine function of these cells. |
| 40 | 16954372 | PD-1 expression was found to be low on naive CD8(+) T cells and increased on memory CD8(+) T cells according to antigen specificity. |
| 41 | 16954372 | Memory CD8(+) T cells specific for poorly controlled chronic persistent virus (HIV) more frequently expressed PD-1 than memory CD8(+) T cells specific for well-controlled persistent virus (cytomegalovirus) or acute (vaccinia) viruses. |
| 42 | 16954372 | PD-1 expression was independent of maturational markers on memory CD8(+) T cells and was not directly associated with an inability to produce cytokines. |
| 43 | 16954372 | Importantly, the level of PD-1 surface expression was the primary determinant of apoptosis sensitivity of virus-specific CD8(+) T cells. |
| 44 | 16954372 | Therefore, PD-1 is a major regulator of apoptosis that can impact the frequency of antiviral T cells in chronic infections such as HIV, and could be manipulated to improve HIV-specific CD8(+) T cell numbers, but possibly not all functions in vivo. |
| 45 | 16954372 | PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection. |
| 46 | 16954372 | Here, we report on the expression of programmed death (PD)-1 on human virus-specific CD8(+) T cells and the effect of manipulating signaling through PD-1 on the survival, proliferation, and cytokine function of these cells. |
| 47 | 16954372 | PD-1 expression was found to be low on naive CD8(+) T cells and increased on memory CD8(+) T cells according to antigen specificity. |
| 48 | 16954372 | Memory CD8(+) T cells specific for poorly controlled chronic persistent virus (HIV) more frequently expressed PD-1 than memory CD8(+) T cells specific for well-controlled persistent virus (cytomegalovirus) or acute (vaccinia) viruses. |
| 49 | 16954372 | PD-1 expression was independent of maturational markers on memory CD8(+) T cells and was not directly associated with an inability to produce cytokines. |
| 50 | 16954372 | Importantly, the level of PD-1 surface expression was the primary determinant of apoptosis sensitivity of virus-specific CD8(+) T cells. |
| 51 | 16954372 | Therefore, PD-1 is a major regulator of apoptosis that can impact the frequency of antiviral T cells in chronic infections such as HIV, and could be manipulated to improve HIV-specific CD8(+) T cell numbers, but possibly not all functions in vivo. |
| 52 | 16954372 | PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection. |
| 53 | 16954372 | Here, we report on the expression of programmed death (PD)-1 on human virus-specific CD8(+) T cells and the effect of manipulating signaling through PD-1 on the survival, proliferation, and cytokine function of these cells. |
| 54 | 16954372 | PD-1 expression was found to be low on naive CD8(+) T cells and increased on memory CD8(+) T cells according to antigen specificity. |
| 55 | 16954372 | Memory CD8(+) T cells specific for poorly controlled chronic persistent virus (HIV) more frequently expressed PD-1 than memory CD8(+) T cells specific for well-controlled persistent virus (cytomegalovirus) or acute (vaccinia) viruses. |
| 56 | 16954372 | PD-1 expression was independent of maturational markers on memory CD8(+) T cells and was not directly associated with an inability to produce cytokines. |
| 57 | 16954372 | Importantly, the level of PD-1 surface expression was the primary determinant of apoptosis sensitivity of virus-specific CD8(+) T cells. |
| 58 | 16954372 | Therefore, PD-1 is a major regulator of apoptosis that can impact the frequency of antiviral T cells in chronic infections such as HIV, and could be manipulated to improve HIV-specific CD8(+) T cell numbers, but possibly not all functions in vivo. |
| 59 | 17376899 | Following infection, the majority (>95%) of Gag-specific CD8 T cells expressed PD-1, and the level of PD-1 expression per cell increased over time. |
| 60 | 17376899 | In vitro blockade of PD-1 resulted in enhanced proliferation of SIV-specific CD8 as well as CD4 T cells. |
| 61 | 17376899 | In contrast, following vaccination, the majority of peak effector Gag-specific CD8 T cells expressed low levels of PD-1, and these levels decreased further as the cells differentiated into memory cells. |
| 62 | 17376899 | In addition, following SHIV challenge of these vaccinated macaques, the level of PD-1 expression on Gag-specific CD8 T cells correlated positively with plasma viremia. |
| 63 | 17376899 | These results demonstrate that SIV-specific CD8 T cells express PD-1 after exposure to antigen but downregulate expression under conditions of antigen clearance and enhance expression under conditions of antigen persistence. |
| 64 | 17376899 | They also demonstrate that the level of PD-1 expression per cell rather than the presence or absence of expression plays an important role in regulating CD8 T-cell dysfunction in pathogenic SIV infection. |
| 65 | 17376899 | Following infection, the majority (>95%) of Gag-specific CD8 T cells expressed PD-1, and the level of PD-1 expression per cell increased over time. |
| 66 | 17376899 | In vitro blockade of PD-1 resulted in enhanced proliferation of SIV-specific CD8 as well as CD4 T cells. |
| 67 | 17376899 | In contrast, following vaccination, the majority of peak effector Gag-specific CD8 T cells expressed low levels of PD-1, and these levels decreased further as the cells differentiated into memory cells. |
| 68 | 17376899 | In addition, following SHIV challenge of these vaccinated macaques, the level of PD-1 expression on Gag-specific CD8 T cells correlated positively with plasma viremia. |
| 69 | 17376899 | These results demonstrate that SIV-specific CD8 T cells express PD-1 after exposure to antigen but downregulate expression under conditions of antigen clearance and enhance expression under conditions of antigen persistence. |
| 70 | 17376899 | They also demonstrate that the level of PD-1 expression per cell rather than the presence or absence of expression plays an important role in regulating CD8 T-cell dysfunction in pathogenic SIV infection. |
| 71 | 17376899 | Following infection, the majority (>95%) of Gag-specific CD8 T cells expressed PD-1, and the level of PD-1 expression per cell increased over time. |
| 72 | 17376899 | In vitro blockade of PD-1 resulted in enhanced proliferation of SIV-specific CD8 as well as CD4 T cells. |
| 73 | 17376899 | In contrast, following vaccination, the majority of peak effector Gag-specific CD8 T cells expressed low levels of PD-1, and these levels decreased further as the cells differentiated into memory cells. |
| 74 | 17376899 | In addition, following SHIV challenge of these vaccinated macaques, the level of PD-1 expression on Gag-specific CD8 T cells correlated positively with plasma viremia. |
| 75 | 17376899 | These results demonstrate that SIV-specific CD8 T cells express PD-1 after exposure to antigen but downregulate expression under conditions of antigen clearance and enhance expression under conditions of antigen persistence. |
| 76 | 17376899 | They also demonstrate that the level of PD-1 expression per cell rather than the presence or absence of expression plays an important role in regulating CD8 T-cell dysfunction in pathogenic SIV infection. |
| 77 | 17376899 | Following infection, the majority (>95%) of Gag-specific CD8 T cells expressed PD-1, and the level of PD-1 expression per cell increased over time. |
| 78 | 17376899 | In vitro blockade of PD-1 resulted in enhanced proliferation of SIV-specific CD8 as well as CD4 T cells. |
| 79 | 17376899 | In contrast, following vaccination, the majority of peak effector Gag-specific CD8 T cells expressed low levels of PD-1, and these levels decreased further as the cells differentiated into memory cells. |
| 80 | 17376899 | In addition, following SHIV challenge of these vaccinated macaques, the level of PD-1 expression on Gag-specific CD8 T cells correlated positively with plasma viremia. |
| 81 | 17376899 | These results demonstrate that SIV-specific CD8 T cells express PD-1 after exposure to antigen but downregulate expression under conditions of antigen clearance and enhance expression under conditions of antigen persistence. |
| 82 | 17376899 | They also demonstrate that the level of PD-1 expression per cell rather than the presence or absence of expression plays an important role in regulating CD8 T-cell dysfunction in pathogenic SIV infection. |
| 83 | 17376899 | Following infection, the majority (>95%) of Gag-specific CD8 T cells expressed PD-1, and the level of PD-1 expression per cell increased over time. |
| 84 | 17376899 | In vitro blockade of PD-1 resulted in enhanced proliferation of SIV-specific CD8 as well as CD4 T cells. |
| 85 | 17376899 | In contrast, following vaccination, the majority of peak effector Gag-specific CD8 T cells expressed low levels of PD-1, and these levels decreased further as the cells differentiated into memory cells. |
| 86 | 17376899 | In addition, following SHIV challenge of these vaccinated macaques, the level of PD-1 expression on Gag-specific CD8 T cells correlated positively with plasma viremia. |
| 87 | 17376899 | These results demonstrate that SIV-specific CD8 T cells express PD-1 after exposure to antigen but downregulate expression under conditions of antigen clearance and enhance expression under conditions of antigen persistence. |
| 88 | 17376899 | They also demonstrate that the level of PD-1 expression per cell rather than the presence or absence of expression plays an important role in regulating CD8 T-cell dysfunction in pathogenic SIV infection. |
| 89 | 17376899 | Following infection, the majority (>95%) of Gag-specific CD8 T cells expressed PD-1, and the level of PD-1 expression per cell increased over time. |
| 90 | 17376899 | In vitro blockade of PD-1 resulted in enhanced proliferation of SIV-specific CD8 as well as CD4 T cells. |
| 91 | 17376899 | In contrast, following vaccination, the majority of peak effector Gag-specific CD8 T cells expressed low levels of PD-1, and these levels decreased further as the cells differentiated into memory cells. |
| 92 | 17376899 | In addition, following SHIV challenge of these vaccinated macaques, the level of PD-1 expression on Gag-specific CD8 T cells correlated positively with plasma viremia. |
| 93 | 17376899 | These results demonstrate that SIV-specific CD8 T cells express PD-1 after exposure to antigen but downregulate expression under conditions of antigen clearance and enhance expression under conditions of antigen persistence. |
| 94 | 17376899 | They also demonstrate that the level of PD-1 expression per cell rather than the presence or absence of expression plays an important role in regulating CD8 T-cell dysfunction in pathogenic SIV infection. |
| 95 | 17440051 | SIV-specific CD8+ T cells express high levels of PD1 and cytokines but have impaired proliferative capacity in acute and chronic SIVmac251 infection. |
| 96 | 17440051 | Programmed death-1 (PD-1) is a critical mediator of virus-specific CD8+ T-cell exhaustion. |
| 97 | 17440051 | Here, we examined the expression of PD-1 on simian immunodeficiency virus (SIV)-specific CD8+ T cells and its possible involvement in regulation of cytokine production, proliferation, and survival of these cells. |
| 98 | 17440051 | The majority of SIV-specific CD8+ T cells expressed a PD-1(high) phenotype, independent of their differentiation status, in all tissues tested. |
| 99 | 17440051 | PD-1 expression gradually declined on CD8+ T cells specific for SIV-derived epitopes that had undergone mutational escape, indicating that antigen-specific TCR stimulation is the primary determinant of PD-1 expression. |
| 100 | 17440051 | SIV-specific PD-1(high)CD8+ T cells produced IFN-gamma, TNF-alpha, and IL-2 under cognate peptide stimulation. |
| 101 | 17440051 | While CD8+ T cells that proliferated in response to antigen had a PD-1(high) phenotype, it was determined that there was a reduced proliferative capacity of PD-1(high) compared with PD-1(low) SIV-specific CD8+ T cells. |
| 102 | 17440051 | PD-1(high) SIV-specific CD8+ T cells were highly susceptible to cell death leading to loss of such cells after in vitro stimulation. |
| 103 | 17440051 | Thus, PD-1 is a negative regulator of SIV-specific CD8+ T cells, operating predominantly through the induction of cell death. |
| 104 | 17440051 | Manipulation of the interaction of PD-1 with its ligands could thus potentially restore the CD8+ T-cell responses in SIV infection. |
| 105 | 17440051 | SIV-specific CD8+ T cells express high levels of PD1 and cytokines but have impaired proliferative capacity in acute and chronic SIVmac251 infection. |
| 106 | 17440051 | Programmed death-1 (PD-1) is a critical mediator of virus-specific CD8+ T-cell exhaustion. |
| 107 | 17440051 | Here, we examined the expression of PD-1 on simian immunodeficiency virus (SIV)-specific CD8+ T cells and its possible involvement in regulation of cytokine production, proliferation, and survival of these cells. |
| 108 | 17440051 | The majority of SIV-specific CD8+ T cells expressed a PD-1(high) phenotype, independent of their differentiation status, in all tissues tested. |
| 109 | 17440051 | PD-1 expression gradually declined on CD8+ T cells specific for SIV-derived epitopes that had undergone mutational escape, indicating that antigen-specific TCR stimulation is the primary determinant of PD-1 expression. |
| 110 | 17440051 | SIV-specific PD-1(high)CD8+ T cells produced IFN-gamma, TNF-alpha, and IL-2 under cognate peptide stimulation. |
| 111 | 17440051 | While CD8+ T cells that proliferated in response to antigen had a PD-1(high) phenotype, it was determined that there was a reduced proliferative capacity of PD-1(high) compared with PD-1(low) SIV-specific CD8+ T cells. |
| 112 | 17440051 | PD-1(high) SIV-specific CD8+ T cells were highly susceptible to cell death leading to loss of such cells after in vitro stimulation. |
| 113 | 17440051 | Thus, PD-1 is a negative regulator of SIV-specific CD8+ T cells, operating predominantly through the induction of cell death. |
| 114 | 17440051 | Manipulation of the interaction of PD-1 with its ligands could thus potentially restore the CD8+ T-cell responses in SIV infection. |
| 115 | 17440051 | SIV-specific CD8+ T cells express high levels of PD1 and cytokines but have impaired proliferative capacity in acute and chronic SIVmac251 infection. |
| 116 | 17440051 | Programmed death-1 (PD-1) is a critical mediator of virus-specific CD8+ T-cell exhaustion. |
| 117 | 17440051 | Here, we examined the expression of PD-1 on simian immunodeficiency virus (SIV)-specific CD8+ T cells and its possible involvement in regulation of cytokine production, proliferation, and survival of these cells. |
| 118 | 17440051 | The majority of SIV-specific CD8+ T cells expressed a PD-1(high) phenotype, independent of their differentiation status, in all tissues tested. |
| 119 | 17440051 | PD-1 expression gradually declined on CD8+ T cells specific for SIV-derived epitopes that had undergone mutational escape, indicating that antigen-specific TCR stimulation is the primary determinant of PD-1 expression. |
| 120 | 17440051 | SIV-specific PD-1(high)CD8+ T cells produced IFN-gamma, TNF-alpha, and IL-2 under cognate peptide stimulation. |
| 121 | 17440051 | While CD8+ T cells that proliferated in response to antigen had a PD-1(high) phenotype, it was determined that there was a reduced proliferative capacity of PD-1(high) compared with PD-1(low) SIV-specific CD8+ T cells. |
| 122 | 17440051 | PD-1(high) SIV-specific CD8+ T cells were highly susceptible to cell death leading to loss of such cells after in vitro stimulation. |
| 123 | 17440051 | Thus, PD-1 is a negative regulator of SIV-specific CD8+ T cells, operating predominantly through the induction of cell death. |
| 124 | 17440051 | Manipulation of the interaction of PD-1 with its ligands could thus potentially restore the CD8+ T-cell responses in SIV infection. |
| 125 | 17440051 | SIV-specific CD8+ T cells express high levels of PD1 and cytokines but have impaired proliferative capacity in acute and chronic SIVmac251 infection. |
| 126 | 17440051 | Programmed death-1 (PD-1) is a critical mediator of virus-specific CD8+ T-cell exhaustion. |
| 127 | 17440051 | Here, we examined the expression of PD-1 on simian immunodeficiency virus (SIV)-specific CD8+ T cells and its possible involvement in regulation of cytokine production, proliferation, and survival of these cells. |
| 128 | 17440051 | The majority of SIV-specific CD8+ T cells expressed a PD-1(high) phenotype, independent of their differentiation status, in all tissues tested. |
| 129 | 17440051 | PD-1 expression gradually declined on CD8+ T cells specific for SIV-derived epitopes that had undergone mutational escape, indicating that antigen-specific TCR stimulation is the primary determinant of PD-1 expression. |
| 130 | 17440051 | SIV-specific PD-1(high)CD8+ T cells produced IFN-gamma, TNF-alpha, and IL-2 under cognate peptide stimulation. |
| 131 | 17440051 | While CD8+ T cells that proliferated in response to antigen had a PD-1(high) phenotype, it was determined that there was a reduced proliferative capacity of PD-1(high) compared with PD-1(low) SIV-specific CD8+ T cells. |
| 132 | 17440051 | PD-1(high) SIV-specific CD8+ T cells were highly susceptible to cell death leading to loss of such cells after in vitro stimulation. |
| 133 | 17440051 | Thus, PD-1 is a negative regulator of SIV-specific CD8+ T cells, operating predominantly through the induction of cell death. |
| 134 | 17440051 | Manipulation of the interaction of PD-1 with its ligands could thus potentially restore the CD8+ T-cell responses in SIV infection. |
| 135 | 17440051 | SIV-specific CD8+ T cells express high levels of PD1 and cytokines but have impaired proliferative capacity in acute and chronic SIVmac251 infection. |
| 136 | 17440051 | Programmed death-1 (PD-1) is a critical mediator of virus-specific CD8+ T-cell exhaustion. |
| 137 | 17440051 | Here, we examined the expression of PD-1 on simian immunodeficiency virus (SIV)-specific CD8+ T cells and its possible involvement in regulation of cytokine production, proliferation, and survival of these cells. |
| 138 | 17440051 | The majority of SIV-specific CD8+ T cells expressed a PD-1(high) phenotype, independent of their differentiation status, in all tissues tested. |
| 139 | 17440051 | PD-1 expression gradually declined on CD8+ T cells specific for SIV-derived epitopes that had undergone mutational escape, indicating that antigen-specific TCR stimulation is the primary determinant of PD-1 expression. |
| 140 | 17440051 | SIV-specific PD-1(high)CD8+ T cells produced IFN-gamma, TNF-alpha, and IL-2 under cognate peptide stimulation. |
| 141 | 17440051 | While CD8+ T cells that proliferated in response to antigen had a PD-1(high) phenotype, it was determined that there was a reduced proliferative capacity of PD-1(high) compared with PD-1(low) SIV-specific CD8+ T cells. |
| 142 | 17440051 | PD-1(high) SIV-specific CD8+ T cells were highly susceptible to cell death leading to loss of such cells after in vitro stimulation. |
| 143 | 17440051 | Thus, PD-1 is a negative regulator of SIV-specific CD8+ T cells, operating predominantly through the induction of cell death. |
| 144 | 17440051 | Manipulation of the interaction of PD-1 with its ligands could thus potentially restore the CD8+ T-cell responses in SIV infection. |
| 145 | 17440051 | SIV-specific CD8+ T cells express high levels of PD1 and cytokines but have impaired proliferative capacity in acute and chronic SIVmac251 infection. |
| 146 | 17440051 | Programmed death-1 (PD-1) is a critical mediator of virus-specific CD8+ T-cell exhaustion. |
| 147 | 17440051 | Here, we examined the expression of PD-1 on simian immunodeficiency virus (SIV)-specific CD8+ T cells and its possible involvement in regulation of cytokine production, proliferation, and survival of these cells. |
| 148 | 17440051 | The majority of SIV-specific CD8+ T cells expressed a PD-1(high) phenotype, independent of their differentiation status, in all tissues tested. |
| 149 | 17440051 | PD-1 expression gradually declined on CD8+ T cells specific for SIV-derived epitopes that had undergone mutational escape, indicating that antigen-specific TCR stimulation is the primary determinant of PD-1 expression. |
| 150 | 17440051 | SIV-specific PD-1(high)CD8+ T cells produced IFN-gamma, TNF-alpha, and IL-2 under cognate peptide stimulation. |
| 151 | 17440051 | While CD8+ T cells that proliferated in response to antigen had a PD-1(high) phenotype, it was determined that there was a reduced proliferative capacity of PD-1(high) compared with PD-1(low) SIV-specific CD8+ T cells. |
| 152 | 17440051 | PD-1(high) SIV-specific CD8+ T cells were highly susceptible to cell death leading to loss of such cells after in vitro stimulation. |
| 153 | 17440051 | Thus, PD-1 is a negative regulator of SIV-specific CD8+ T cells, operating predominantly through the induction of cell death. |
| 154 | 17440051 | Manipulation of the interaction of PD-1 with its ligands could thus potentially restore the CD8+ T-cell responses in SIV infection. |
| 155 | 17440051 | SIV-specific CD8+ T cells express high levels of PD1 and cytokines but have impaired proliferative capacity in acute and chronic SIVmac251 infection. |
| 156 | 17440051 | Programmed death-1 (PD-1) is a critical mediator of virus-specific CD8+ T-cell exhaustion. |
| 157 | 17440051 | Here, we examined the expression of PD-1 on simian immunodeficiency virus (SIV)-specific CD8+ T cells and its possible involvement in regulation of cytokine production, proliferation, and survival of these cells. |
| 158 | 17440051 | The majority of SIV-specific CD8+ T cells expressed a PD-1(high) phenotype, independent of their differentiation status, in all tissues tested. |
| 159 | 17440051 | PD-1 expression gradually declined on CD8+ T cells specific for SIV-derived epitopes that had undergone mutational escape, indicating that antigen-specific TCR stimulation is the primary determinant of PD-1 expression. |
| 160 | 17440051 | SIV-specific PD-1(high)CD8+ T cells produced IFN-gamma, TNF-alpha, and IL-2 under cognate peptide stimulation. |
| 161 | 17440051 | While CD8+ T cells that proliferated in response to antigen had a PD-1(high) phenotype, it was determined that there was a reduced proliferative capacity of PD-1(high) compared with PD-1(low) SIV-specific CD8+ T cells. |
| 162 | 17440051 | PD-1(high) SIV-specific CD8+ T cells were highly susceptible to cell death leading to loss of such cells after in vitro stimulation. |
| 163 | 17440051 | Thus, PD-1 is a negative regulator of SIV-specific CD8+ T cells, operating predominantly through the induction of cell death. |
| 164 | 17440051 | Manipulation of the interaction of PD-1 with its ligands could thus potentially restore the CD8+ T-cell responses in SIV infection. |
| 165 | 17440051 | SIV-specific CD8+ T cells express high levels of PD1 and cytokines but have impaired proliferative capacity in acute and chronic SIVmac251 infection. |
| 166 | 17440051 | Programmed death-1 (PD-1) is a critical mediator of virus-specific CD8+ T-cell exhaustion. |
| 167 | 17440051 | Here, we examined the expression of PD-1 on simian immunodeficiency virus (SIV)-specific CD8+ T cells and its possible involvement in regulation of cytokine production, proliferation, and survival of these cells. |
| 168 | 17440051 | The majority of SIV-specific CD8+ T cells expressed a PD-1(high) phenotype, independent of their differentiation status, in all tissues tested. |
| 169 | 17440051 | PD-1 expression gradually declined on CD8+ T cells specific for SIV-derived epitopes that had undergone mutational escape, indicating that antigen-specific TCR stimulation is the primary determinant of PD-1 expression. |
| 170 | 17440051 | SIV-specific PD-1(high)CD8+ T cells produced IFN-gamma, TNF-alpha, and IL-2 under cognate peptide stimulation. |
| 171 | 17440051 | While CD8+ T cells that proliferated in response to antigen had a PD-1(high) phenotype, it was determined that there was a reduced proliferative capacity of PD-1(high) compared with PD-1(low) SIV-specific CD8+ T cells. |
| 172 | 17440051 | PD-1(high) SIV-specific CD8+ T cells were highly susceptible to cell death leading to loss of such cells after in vitro stimulation. |
| 173 | 17440051 | Thus, PD-1 is a negative regulator of SIV-specific CD8+ T cells, operating predominantly through the induction of cell death. |
| 174 | 17440051 | Manipulation of the interaction of PD-1 with its ligands could thus potentially restore the CD8+ T-cell responses in SIV infection. |
| 175 | 17440051 | SIV-specific CD8+ T cells express high levels of PD1 and cytokines but have impaired proliferative capacity in acute and chronic SIVmac251 infection. |
| 176 | 17440051 | Programmed death-1 (PD-1) is a critical mediator of virus-specific CD8+ T-cell exhaustion. |
| 177 | 17440051 | Here, we examined the expression of PD-1 on simian immunodeficiency virus (SIV)-specific CD8+ T cells and its possible involvement in regulation of cytokine production, proliferation, and survival of these cells. |
| 178 | 17440051 | The majority of SIV-specific CD8+ T cells expressed a PD-1(high) phenotype, independent of their differentiation status, in all tissues tested. |
| 179 | 17440051 | PD-1 expression gradually declined on CD8+ T cells specific for SIV-derived epitopes that had undergone mutational escape, indicating that antigen-specific TCR stimulation is the primary determinant of PD-1 expression. |
| 180 | 17440051 | SIV-specific PD-1(high)CD8+ T cells produced IFN-gamma, TNF-alpha, and IL-2 under cognate peptide stimulation. |
| 181 | 17440051 | While CD8+ T cells that proliferated in response to antigen had a PD-1(high) phenotype, it was determined that there was a reduced proliferative capacity of PD-1(high) compared with PD-1(low) SIV-specific CD8+ T cells. |
| 182 | 17440051 | PD-1(high) SIV-specific CD8+ T cells were highly susceptible to cell death leading to loss of such cells after in vitro stimulation. |
| 183 | 17440051 | Thus, PD-1 is a negative regulator of SIV-specific CD8+ T cells, operating predominantly through the induction of cell death. |
| 184 | 17440051 | Manipulation of the interaction of PD-1 with its ligands could thus potentially restore the CD8+ T-cell responses in SIV infection. |
| 185 | 17440051 | SIV-specific CD8+ T cells express high levels of PD1 and cytokines but have impaired proliferative capacity in acute and chronic SIVmac251 infection. |
| 186 | 17440051 | Programmed death-1 (PD-1) is a critical mediator of virus-specific CD8+ T-cell exhaustion. |
| 187 | 17440051 | Here, we examined the expression of PD-1 on simian immunodeficiency virus (SIV)-specific CD8+ T cells and its possible involvement in regulation of cytokine production, proliferation, and survival of these cells. |
| 188 | 17440051 | The majority of SIV-specific CD8+ T cells expressed a PD-1(high) phenotype, independent of their differentiation status, in all tissues tested. |
| 189 | 17440051 | PD-1 expression gradually declined on CD8+ T cells specific for SIV-derived epitopes that had undergone mutational escape, indicating that antigen-specific TCR stimulation is the primary determinant of PD-1 expression. |
| 190 | 17440051 | SIV-specific PD-1(high)CD8+ T cells produced IFN-gamma, TNF-alpha, and IL-2 under cognate peptide stimulation. |
| 191 | 17440051 | While CD8+ T cells that proliferated in response to antigen had a PD-1(high) phenotype, it was determined that there was a reduced proliferative capacity of PD-1(high) compared with PD-1(low) SIV-specific CD8+ T cells. |
| 192 | 17440051 | PD-1(high) SIV-specific CD8+ T cells were highly susceptible to cell death leading to loss of such cells after in vitro stimulation. |
| 193 | 17440051 | Thus, PD-1 is a negative regulator of SIV-specific CD8+ T cells, operating predominantly through the induction of cell death. |
| 194 | 17440051 | Manipulation of the interaction of PD-1 with its ligands could thus potentially restore the CD8+ T-cell responses in SIV infection. |
| 195 | 17898045 | In this study, we examined the effects of a fully human PD-1-abrogating antibody on the in vitro expansion and function of human vaccine-induced CD8+ T cells (CTLs) specific for the melanoma-associated antigens glycoprotein 100 (gp100) and melanoma antigen recognized by T cells (MART)-1. |
| 196 | 17898045 | PD-1 blockade during peptide stimulation augmented the absolute numbers of CD3+, CD4+, CD8+ and gp100/MART-1 MHC:peptide tetramer+ CTLs. |
| 197 | 17898045 | This correlated with increased frequencies of IFN-gamma-secreting antigen-specific cells and augmented lysis of gp100+/MART-1+ melanoma targets. |
| 198 | 17950003 | These data showed that exhausted CD8(+) T cells: (1) overexpressed several inhibitory receptors, including PD-1, (2) had major changes in T cell receptor and cytokine signaling pathways, (3) displayed altered expression of genes involved in chemotaxis, adhesion, and migration, (4) expressed a distinct set of transcription factors, and (5) had profound metabolic and bioenergetic deficiencies. |
| 199 | 18161757 | In addition, sterile cure may be achieved with minimal side-effects by combining agents that alter the IL-10 signalling pathway with other compounds, such as antiviral drugs or interferon, but also agents neutralizing other crucial elements of T cell exhaustion, such as PD-1. |
| 200 | 18171281 | PD-1 levels were measured among the total population of CD8(+) and CD8(+) T cells binding to CMV-specific major histocompatibility complex class I tetramers. |
| 201 | 18337576 | The inhibitory receptor programmed death-1 (PD-1) is present on CD8(+) T cells in chronic hepatitis C virus (HCV), but expression patterns in spontaneously resolving infections are incompletely characterized. |
| 202 | 18337576 | Here we report that PD-1 was usually absent on memory CD8(+) T cells from chimpanzees with resolved infections, but sustained low-level expression was sometimes observed in the absence of apparent virus replication. |
| 203 | 18337576 | The inhibitory receptor programmed death-1 (PD-1) is present on CD8(+) T cells in chronic hepatitis C virus (HCV), but expression patterns in spontaneously resolving infections are incompletely characterized. |
| 204 | 18337576 | Here we report that PD-1 was usually absent on memory CD8(+) T cells from chimpanzees with resolved infections, but sustained low-level expression was sometimes observed in the absence of apparent virus replication. |
| 205 | 18389475 | Ex vivo peptide stimulation of PBMC from DNA-vaccinated uninfected macaques revealed a temporal increase in PD-1 expression in proliferating antigen-specific CD8(+) T cells. |
| 206 | 18389475 | Following the initial increase, PD-1 expression steadily declined as proliferation continued, with a concomitant increase in IFN-gamma secretion. |
| 207 | 18389475 | Ex vivo peptide stimulation of PBMC from DNA-vaccinated uninfected macaques revealed a temporal increase in PD-1 expression in proliferating antigen-specific CD8(+) T cells. |
| 208 | 18389475 | Following the initial increase, PD-1 expression steadily declined as proliferation continued, with a concomitant increase in IFN-gamma secretion. |
| 209 | 18523260 | Therapeutic vaccination with simian immunodeficiency virus (SIV)-DNA + IL-12 or IL-15 induces distinct CD8 memory subsets in SIV-infected macaques. |
| 210 | 18523260 | Cytokines, such as IL-12 and IL-15, have been shown to be potent adjuvants for the induction and maintenance of cellular immune responses, in particular during HIV infection. |
| 211 | 18523260 | In this study, we examined the ability of therapeutic vaccination with SIV-DNA+IL-12 or IL-15 as molecular adjuvants to improve DNA vaccine potency and to enhance memory immune responses in SIV-infected macaques. |
| 212 | 18523260 | Our results demonstrate that incorporating IL-12 into the vaccine induces SIV-specific CD8 effector memory T cell (T(EM)) functional responses and enhances the capacity of IFN-gamma-producing CD8 T(EM) cells to produce TNF. |
| 213 | 18523260 | Lower levels of PD-1 were expressed on T cells acquiring dual function upon vaccination as compared with mono-functional CD8 T(EM) cells. |
| 214 | 18523260 | Finally, a boost with SIV-DNA+IL-15 triggered most T cell memory subsets in macaques primed with either DNA-SIV or placebo but only CD8 T(EM) in macaques primed with SIV-DNA+IL-12. |
| 215 | 18523260 | These results indicate that plasmid IL-12 and IL-15 cytokines represent a significant addition to enhance the ability of therapeutic DNA vaccines to induce better immunity. |
| 216 | 18707923 | Expression of PD-1 is up-regulated in CD4+CD25+ FoxP3+ regulatory T cell of non-responders after hepatitis B surface antigen vaccine immunization. |
| 217 | 19043418 | Regulation of T cell exhaustion by various inhibitory pathways was nonredundant, as blockade of the T cell inhibitory receptors PD-1 and LAG-3 simultaneously and synergistically improved T cell responses and diminished viral load in vivo. |
| 218 | 19211743 | Impact of epitope escape on PD-1 expression and CD8 T-cell exhaustion during chronic infection. |
| 219 | 19211743 | Viral clearance results in PD-1(lo) functional virus-specific CD8 T cells, while the persistence of wild-type LCMV results in high PD-1 levels and T-cell exhaustion. |
| 220 | 19211743 | However, following the emergence of a GP35V-->A variant virus that abrogates the presentation of the GP33 epitope, GP33-specific CD8 T cells remained functional, continued to show low levels of PD-1, and reexpressed CD127, a marker of memory T-cell differentiation. |
| 221 | 19211743 | In the same animals and under identical environmental conditions, CD8 T cells recognizing nonmutated viral epitopes became physically deleted or were PD-1(hi) and nonfunctional. |
| 222 | 19211743 | Impact of epitope escape on PD-1 expression and CD8 T-cell exhaustion during chronic infection. |
| 223 | 19211743 | Viral clearance results in PD-1(lo) functional virus-specific CD8 T cells, while the persistence of wild-type LCMV results in high PD-1 levels and T-cell exhaustion. |
| 224 | 19211743 | However, following the emergence of a GP35V-->A variant virus that abrogates the presentation of the GP33 epitope, GP33-specific CD8 T cells remained functional, continued to show low levels of PD-1, and reexpressed CD127, a marker of memory T-cell differentiation. |
| 225 | 19211743 | In the same animals and under identical environmental conditions, CD8 T cells recognizing nonmutated viral epitopes became physically deleted or were PD-1(hi) and nonfunctional. |
| 226 | 19211743 | Impact of epitope escape on PD-1 expression and CD8 T-cell exhaustion during chronic infection. |
| 227 | 19211743 | Viral clearance results in PD-1(lo) functional virus-specific CD8 T cells, while the persistence of wild-type LCMV results in high PD-1 levels and T-cell exhaustion. |
| 228 | 19211743 | However, following the emergence of a GP35V-->A variant virus that abrogates the presentation of the GP33 epitope, GP33-specific CD8 T cells remained functional, continued to show low levels of PD-1, and reexpressed CD127, a marker of memory T-cell differentiation. |
| 229 | 19211743 | In the same animals and under identical environmental conditions, CD8 T cells recognizing nonmutated viral epitopes became physically deleted or were PD-1(hi) and nonfunctional. |
| 230 | 19211743 | Impact of epitope escape on PD-1 expression and CD8 T-cell exhaustion during chronic infection. |
| 231 | 19211743 | Viral clearance results in PD-1(lo) functional virus-specific CD8 T cells, while the persistence of wild-type LCMV results in high PD-1 levels and T-cell exhaustion. |
| 232 | 19211743 | However, following the emergence of a GP35V-->A variant virus that abrogates the presentation of the GP33 epitope, GP33-specific CD8 T cells remained functional, continued to show low levels of PD-1, and reexpressed CD127, a marker of memory T-cell differentiation. |
| 233 | 19211743 | In the same animals and under identical environmental conditions, CD8 T cells recognizing nonmutated viral epitopes became physically deleted or were PD-1(hi) and nonfunctional. |
| 234 | 19306502 | T cell expression of the inhibitory receptor programmed death-1 (PD-1) and inhibition of effector T cells (Teffs) by CD4+Foxp3+Tregs are among the many described mechanisms for achieving a balanced immune response. |
| 235 | 19306502 | In this issue of the JCI, Franceschini et al. extend our understanding of how Tregs are modulated during chronic HCV infection by demonstrating that Treg proliferation is inhibited by PD-1 and that this inhibition is mediated by a potentially novel mechanism involving the prevention of IL-2-driven STAT-5phosphorylation. |
| 236 | 19306502 | T cell expression of the inhibitory receptor programmed death-1 (PD-1) and inhibition of effector T cells (Teffs) by CD4+Foxp3+Tregs are among the many described mechanisms for achieving a balanced immune response. |
| 237 | 19306502 | In this issue of the JCI, Franceschini et al. extend our understanding of how Tregs are modulated during chronic HCV infection by demonstrating that Treg proliferation is inhibited by PD-1 and that this inhibition is mediated by a potentially novel mechanism involving the prevention of IL-2-driven STAT-5phosphorylation. |
| 238 | 19564339 | Recent studies have revealed the critical role of programmed death-1 (PD-1) in exhaustion of HIV- and SIV-specific CD8(+) T cells. |
| 239 | 19564339 | In this study, we show that high expression of PD-1 correlates with increased ex vivo spontaneous and CD95/Fas-induced apoptosis, particularly in the "effector-memory" CD8(+) T cell population from HIV(+) donors. |
| 240 | 19564339 | High expression of PD-1 was linked to a proapoptotic phenotype characterized by low expression of Bcl-2 and IL7-R alpha, high expression of CD95/Fas and high mitochondrial mass. |
| 241 | 19564339 | Expression of PD-1 and CD57 was differentially associated with the maturation status of CD8(+) T cells in HIV infection. |
| 242 | 19564339 | CD57 was linked to higher apoptosis resistance, with cells expressing a PD-1(L)CD57(H) phenotype exhibiting lower levels of cell death. |
| 243 | 19564339 | The majority of HIV-specific CD8(+) T cells were found to express a PD-1(H)CD57(L) or PD-1(H)CD57(H) phenotype. |
| 244 | 19564339 | No correlation was found between PD-1 expression and ex vivo polyfunctionality of either HIV- or CMV-specific CD8(+) T cells. |
| 245 | 19564339 | Contrary to CD57, high expression of PD-1 was characterized by translocation of PD-1 into the area of CD95/Fas-capping, an early necessary step of CD95/Fas-induced apoptosis. |
| 246 | 19564339 | Thus, our data further support the role of PD-1 as a preapoptotic factor for CD8(+) T cells in HIV infection. |
| 247 | 19564339 | Recent studies have revealed the critical role of programmed death-1 (PD-1) in exhaustion of HIV- and SIV-specific CD8(+) T cells. |
| 248 | 19564339 | In this study, we show that high expression of PD-1 correlates with increased ex vivo spontaneous and CD95/Fas-induced apoptosis, particularly in the "effector-memory" CD8(+) T cell population from HIV(+) donors. |
| 249 | 19564339 | High expression of PD-1 was linked to a proapoptotic phenotype characterized by low expression of Bcl-2 and IL7-R alpha, high expression of CD95/Fas and high mitochondrial mass. |
| 250 | 19564339 | Expression of PD-1 and CD57 was differentially associated with the maturation status of CD8(+) T cells in HIV infection. |
| 251 | 19564339 | CD57 was linked to higher apoptosis resistance, with cells expressing a PD-1(L)CD57(H) phenotype exhibiting lower levels of cell death. |
| 252 | 19564339 | The majority of HIV-specific CD8(+) T cells were found to express a PD-1(H)CD57(L) or PD-1(H)CD57(H) phenotype. |
| 253 | 19564339 | No correlation was found between PD-1 expression and ex vivo polyfunctionality of either HIV- or CMV-specific CD8(+) T cells. |
| 254 | 19564339 | Contrary to CD57, high expression of PD-1 was characterized by translocation of PD-1 into the area of CD95/Fas-capping, an early necessary step of CD95/Fas-induced apoptosis. |
| 255 | 19564339 | Thus, our data further support the role of PD-1 as a preapoptotic factor for CD8(+) T cells in HIV infection. |
| 256 | 19564339 | Recent studies have revealed the critical role of programmed death-1 (PD-1) in exhaustion of HIV- and SIV-specific CD8(+) T cells. |
| 257 | 19564339 | In this study, we show that high expression of PD-1 correlates with increased ex vivo spontaneous and CD95/Fas-induced apoptosis, particularly in the "effector-memory" CD8(+) T cell population from HIV(+) donors. |
| 258 | 19564339 | High expression of PD-1 was linked to a proapoptotic phenotype characterized by low expression of Bcl-2 and IL7-R alpha, high expression of CD95/Fas and high mitochondrial mass. |
| 259 | 19564339 | Expression of PD-1 and CD57 was differentially associated with the maturation status of CD8(+) T cells in HIV infection. |
| 260 | 19564339 | CD57 was linked to higher apoptosis resistance, with cells expressing a PD-1(L)CD57(H) phenotype exhibiting lower levels of cell death. |
| 261 | 19564339 | The majority of HIV-specific CD8(+) T cells were found to express a PD-1(H)CD57(L) or PD-1(H)CD57(H) phenotype. |
| 262 | 19564339 | No correlation was found between PD-1 expression and ex vivo polyfunctionality of either HIV- or CMV-specific CD8(+) T cells. |
| 263 | 19564339 | Contrary to CD57, high expression of PD-1 was characterized by translocation of PD-1 into the area of CD95/Fas-capping, an early necessary step of CD95/Fas-induced apoptosis. |
| 264 | 19564339 | Thus, our data further support the role of PD-1 as a preapoptotic factor for CD8(+) T cells in HIV infection. |
| 265 | 19564339 | Recent studies have revealed the critical role of programmed death-1 (PD-1) in exhaustion of HIV- and SIV-specific CD8(+) T cells. |
| 266 | 19564339 | In this study, we show that high expression of PD-1 correlates with increased ex vivo spontaneous and CD95/Fas-induced apoptosis, particularly in the "effector-memory" CD8(+) T cell population from HIV(+) donors. |
| 267 | 19564339 | High expression of PD-1 was linked to a proapoptotic phenotype characterized by low expression of Bcl-2 and IL7-R alpha, high expression of CD95/Fas and high mitochondrial mass. |
| 268 | 19564339 | Expression of PD-1 and CD57 was differentially associated with the maturation status of CD8(+) T cells in HIV infection. |
| 269 | 19564339 | CD57 was linked to higher apoptosis resistance, with cells expressing a PD-1(L)CD57(H) phenotype exhibiting lower levels of cell death. |
| 270 | 19564339 | The majority of HIV-specific CD8(+) T cells were found to express a PD-1(H)CD57(L) or PD-1(H)CD57(H) phenotype. |
| 271 | 19564339 | No correlation was found between PD-1 expression and ex vivo polyfunctionality of either HIV- or CMV-specific CD8(+) T cells. |
| 272 | 19564339 | Contrary to CD57, high expression of PD-1 was characterized by translocation of PD-1 into the area of CD95/Fas-capping, an early necessary step of CD95/Fas-induced apoptosis. |
| 273 | 19564339 | Thus, our data further support the role of PD-1 as a preapoptotic factor for CD8(+) T cells in HIV infection. |
| 274 | 19564339 | Recent studies have revealed the critical role of programmed death-1 (PD-1) in exhaustion of HIV- and SIV-specific CD8(+) T cells. |
| 275 | 19564339 | In this study, we show that high expression of PD-1 correlates with increased ex vivo spontaneous and CD95/Fas-induced apoptosis, particularly in the "effector-memory" CD8(+) T cell population from HIV(+) donors. |
| 276 | 19564339 | High expression of PD-1 was linked to a proapoptotic phenotype characterized by low expression of Bcl-2 and IL7-R alpha, high expression of CD95/Fas and high mitochondrial mass. |
| 277 | 19564339 | Expression of PD-1 and CD57 was differentially associated with the maturation status of CD8(+) T cells in HIV infection. |
| 278 | 19564339 | CD57 was linked to higher apoptosis resistance, with cells expressing a PD-1(L)CD57(H) phenotype exhibiting lower levels of cell death. |
| 279 | 19564339 | The majority of HIV-specific CD8(+) T cells were found to express a PD-1(H)CD57(L) or PD-1(H)CD57(H) phenotype. |
| 280 | 19564339 | No correlation was found between PD-1 expression and ex vivo polyfunctionality of either HIV- or CMV-specific CD8(+) T cells. |
| 281 | 19564339 | Contrary to CD57, high expression of PD-1 was characterized by translocation of PD-1 into the area of CD95/Fas-capping, an early necessary step of CD95/Fas-induced apoptosis. |
| 282 | 19564339 | Thus, our data further support the role of PD-1 as a preapoptotic factor for CD8(+) T cells in HIV infection. |
| 283 | 19564339 | Recent studies have revealed the critical role of programmed death-1 (PD-1) in exhaustion of HIV- and SIV-specific CD8(+) T cells. |
| 284 | 19564339 | In this study, we show that high expression of PD-1 correlates with increased ex vivo spontaneous and CD95/Fas-induced apoptosis, particularly in the "effector-memory" CD8(+) T cell population from HIV(+) donors. |
| 285 | 19564339 | High expression of PD-1 was linked to a proapoptotic phenotype characterized by low expression of Bcl-2 and IL7-R alpha, high expression of CD95/Fas and high mitochondrial mass. |
| 286 | 19564339 | Expression of PD-1 and CD57 was differentially associated with the maturation status of CD8(+) T cells in HIV infection. |
| 287 | 19564339 | CD57 was linked to higher apoptosis resistance, with cells expressing a PD-1(L)CD57(H) phenotype exhibiting lower levels of cell death. |
| 288 | 19564339 | The majority of HIV-specific CD8(+) T cells were found to express a PD-1(H)CD57(L) or PD-1(H)CD57(H) phenotype. |
| 289 | 19564339 | No correlation was found between PD-1 expression and ex vivo polyfunctionality of either HIV- or CMV-specific CD8(+) T cells. |
| 290 | 19564339 | Contrary to CD57, high expression of PD-1 was characterized by translocation of PD-1 into the area of CD95/Fas-capping, an early necessary step of CD95/Fas-induced apoptosis. |
| 291 | 19564339 | Thus, our data further support the role of PD-1 as a preapoptotic factor for CD8(+) T cells in HIV infection. |
| 292 | 19564339 | Recent studies have revealed the critical role of programmed death-1 (PD-1) in exhaustion of HIV- and SIV-specific CD8(+) T cells. |
| 293 | 19564339 | In this study, we show that high expression of PD-1 correlates with increased ex vivo spontaneous and CD95/Fas-induced apoptosis, particularly in the "effector-memory" CD8(+) T cell population from HIV(+) donors. |
| 294 | 19564339 | High expression of PD-1 was linked to a proapoptotic phenotype characterized by low expression of Bcl-2 and IL7-R alpha, high expression of CD95/Fas and high mitochondrial mass. |
| 295 | 19564339 | Expression of PD-1 and CD57 was differentially associated with the maturation status of CD8(+) T cells in HIV infection. |
| 296 | 19564339 | CD57 was linked to higher apoptosis resistance, with cells expressing a PD-1(L)CD57(H) phenotype exhibiting lower levels of cell death. |
| 297 | 19564339 | The majority of HIV-specific CD8(+) T cells were found to express a PD-1(H)CD57(L) or PD-1(H)CD57(H) phenotype. |
| 298 | 19564339 | No correlation was found between PD-1 expression and ex vivo polyfunctionality of either HIV- or CMV-specific CD8(+) T cells. |
| 299 | 19564339 | Contrary to CD57, high expression of PD-1 was characterized by translocation of PD-1 into the area of CD95/Fas-capping, an early necessary step of CD95/Fas-induced apoptosis. |
| 300 | 19564339 | Thus, our data further support the role of PD-1 as a preapoptotic factor for CD8(+) T cells in HIV infection. |
| 301 | 19564339 | Recent studies have revealed the critical role of programmed death-1 (PD-1) in exhaustion of HIV- and SIV-specific CD8(+) T cells. |
| 302 | 19564339 | In this study, we show that high expression of PD-1 correlates with increased ex vivo spontaneous and CD95/Fas-induced apoptosis, particularly in the "effector-memory" CD8(+) T cell population from HIV(+) donors. |
| 303 | 19564339 | High expression of PD-1 was linked to a proapoptotic phenotype characterized by low expression of Bcl-2 and IL7-R alpha, high expression of CD95/Fas and high mitochondrial mass. |
| 304 | 19564339 | Expression of PD-1 and CD57 was differentially associated with the maturation status of CD8(+) T cells in HIV infection. |
| 305 | 19564339 | CD57 was linked to higher apoptosis resistance, with cells expressing a PD-1(L)CD57(H) phenotype exhibiting lower levels of cell death. |
| 306 | 19564339 | The majority of HIV-specific CD8(+) T cells were found to express a PD-1(H)CD57(L) or PD-1(H)CD57(H) phenotype. |
| 307 | 19564339 | No correlation was found between PD-1 expression and ex vivo polyfunctionality of either HIV- or CMV-specific CD8(+) T cells. |
| 308 | 19564339 | Contrary to CD57, high expression of PD-1 was characterized by translocation of PD-1 into the area of CD95/Fas-capping, an early necessary step of CD95/Fas-induced apoptosis. |
| 309 | 19564339 | Thus, our data further support the role of PD-1 as a preapoptotic factor for CD8(+) T cells in HIV infection. |
| 310 | 19564339 | Recent studies have revealed the critical role of programmed death-1 (PD-1) in exhaustion of HIV- and SIV-specific CD8(+) T cells. |
| 311 | 19564339 | In this study, we show that high expression of PD-1 correlates with increased ex vivo spontaneous and CD95/Fas-induced apoptosis, particularly in the "effector-memory" CD8(+) T cell population from HIV(+) donors. |
| 312 | 19564339 | High expression of PD-1 was linked to a proapoptotic phenotype characterized by low expression of Bcl-2 and IL7-R alpha, high expression of CD95/Fas and high mitochondrial mass. |
| 313 | 19564339 | Expression of PD-1 and CD57 was differentially associated with the maturation status of CD8(+) T cells in HIV infection. |
| 314 | 19564339 | CD57 was linked to higher apoptosis resistance, with cells expressing a PD-1(L)CD57(H) phenotype exhibiting lower levels of cell death. |
| 315 | 19564339 | The majority of HIV-specific CD8(+) T cells were found to express a PD-1(H)CD57(L) or PD-1(H)CD57(H) phenotype. |
| 316 | 19564339 | No correlation was found between PD-1 expression and ex vivo polyfunctionality of either HIV- or CMV-specific CD8(+) T cells. |
| 317 | 19564339 | Contrary to CD57, high expression of PD-1 was characterized by translocation of PD-1 into the area of CD95/Fas-capping, an early necessary step of CD95/Fas-induced apoptosis. |
| 318 | 19564339 | Thus, our data further support the role of PD-1 as a preapoptotic factor for CD8(+) T cells in HIV infection. |
| 319 | 19651643 | PD1 blockade reverses the suppression of melanoma antigen-specific CTL by CD4+ CD25(Hi) regulatory T cells. |
| 320 | 19651643 | Regulatory CD4(+)CD25(Hi) T cells (Treg) and programmed death-1 (PD-1) molecule have emerged as pivotal players in immune regulation. |
| 321 | 19651643 | We identified Treg in the circulation of vaccinated melanoma patients and detected PD-1 expression on vaccine-induced melanoma antigen-specific CTLs, as well as on and within Treg from patients' peripheral blood. |
| 322 | 19651643 | PD-1 blockade promoted the generation of melanoma antigen-specific CTLs and masked their inhibition by Treg. |
| 323 | 19651643 | The mechanisms by which PD-1 blockade mediated immune enhancement included direct augmentation of melanoma antigen-specific CTL proliferation, heightening their resistance to inhibition by Treg and direct limitation of the inhibitory ability of Treg. |
| 324 | 19651643 | PD-1 blockade reversed the increased expression of PD-1 and PD-L1 on melanoma antigen-specific CTL by Treg, rescued INF-gamma and IL-2 or INF-gamma and tumor necrosis factor-alpha co-expression and expression of IL-7 receptor by melanoma antigen-specific CTL which were diminished by Treg. |
| 325 | 19651643 | PD1 blockade reverses the suppression of melanoma antigen-specific CTL by CD4+ CD25(Hi) regulatory T cells. |
| 326 | 19651643 | Regulatory CD4(+)CD25(Hi) T cells (Treg) and programmed death-1 (PD-1) molecule have emerged as pivotal players in immune regulation. |
| 327 | 19651643 | We identified Treg in the circulation of vaccinated melanoma patients and detected PD-1 expression on vaccine-induced melanoma antigen-specific CTLs, as well as on and within Treg from patients' peripheral blood. |
| 328 | 19651643 | PD-1 blockade promoted the generation of melanoma antigen-specific CTLs and masked their inhibition by Treg. |
| 329 | 19651643 | The mechanisms by which PD-1 blockade mediated immune enhancement included direct augmentation of melanoma antigen-specific CTL proliferation, heightening their resistance to inhibition by Treg and direct limitation of the inhibitory ability of Treg. |
| 330 | 19651643 | PD-1 blockade reversed the increased expression of PD-1 and PD-L1 on melanoma antigen-specific CTL by Treg, rescued INF-gamma and IL-2 or INF-gamma and tumor necrosis factor-alpha co-expression and expression of IL-7 receptor by melanoma antigen-specific CTL which were diminished by Treg. |
| 331 | 19651643 | PD1 blockade reverses the suppression of melanoma antigen-specific CTL by CD4+ CD25(Hi) regulatory T cells. |
| 332 | 19651643 | Regulatory CD4(+)CD25(Hi) T cells (Treg) and programmed death-1 (PD-1) molecule have emerged as pivotal players in immune regulation. |
| 333 | 19651643 | We identified Treg in the circulation of vaccinated melanoma patients and detected PD-1 expression on vaccine-induced melanoma antigen-specific CTLs, as well as on and within Treg from patients' peripheral blood. |
| 334 | 19651643 | PD-1 blockade promoted the generation of melanoma antigen-specific CTLs and masked their inhibition by Treg. |
| 335 | 19651643 | The mechanisms by which PD-1 blockade mediated immune enhancement included direct augmentation of melanoma antigen-specific CTL proliferation, heightening their resistance to inhibition by Treg and direct limitation of the inhibitory ability of Treg. |
| 336 | 19651643 | PD-1 blockade reversed the increased expression of PD-1 and PD-L1 on melanoma antigen-specific CTL by Treg, rescued INF-gamma and IL-2 or INF-gamma and tumor necrosis factor-alpha co-expression and expression of IL-7 receptor by melanoma antigen-specific CTL which were diminished by Treg. |
| 337 | 19651643 | PD1 blockade reverses the suppression of melanoma antigen-specific CTL by CD4+ CD25(Hi) regulatory T cells. |
| 338 | 19651643 | Regulatory CD4(+)CD25(Hi) T cells (Treg) and programmed death-1 (PD-1) molecule have emerged as pivotal players in immune regulation. |
| 339 | 19651643 | We identified Treg in the circulation of vaccinated melanoma patients and detected PD-1 expression on vaccine-induced melanoma antigen-specific CTLs, as well as on and within Treg from patients' peripheral blood. |
| 340 | 19651643 | PD-1 blockade promoted the generation of melanoma antigen-specific CTLs and masked their inhibition by Treg. |
| 341 | 19651643 | The mechanisms by which PD-1 blockade mediated immune enhancement included direct augmentation of melanoma antigen-specific CTL proliferation, heightening their resistance to inhibition by Treg and direct limitation of the inhibitory ability of Treg. |
| 342 | 19651643 | PD-1 blockade reversed the increased expression of PD-1 and PD-L1 on melanoma antigen-specific CTL by Treg, rescued INF-gamma and IL-2 or INF-gamma and tumor necrosis factor-alpha co-expression and expression of IL-7 receptor by melanoma antigen-specific CTL which were diminished by Treg. |
| 343 | 19651643 | PD1 blockade reverses the suppression of melanoma antigen-specific CTL by CD4+ CD25(Hi) regulatory T cells. |
| 344 | 19651643 | Regulatory CD4(+)CD25(Hi) T cells (Treg) and programmed death-1 (PD-1) molecule have emerged as pivotal players in immune regulation. |
| 345 | 19651643 | We identified Treg in the circulation of vaccinated melanoma patients and detected PD-1 expression on vaccine-induced melanoma antigen-specific CTLs, as well as on and within Treg from patients' peripheral blood. |
| 346 | 19651643 | PD-1 blockade promoted the generation of melanoma antigen-specific CTLs and masked their inhibition by Treg. |
| 347 | 19651643 | The mechanisms by which PD-1 blockade mediated immune enhancement included direct augmentation of melanoma antigen-specific CTL proliferation, heightening their resistance to inhibition by Treg and direct limitation of the inhibitory ability of Treg. |
| 348 | 19651643 | PD-1 blockade reversed the increased expression of PD-1 and PD-L1 on melanoma antigen-specific CTL by Treg, rescued INF-gamma and IL-2 or INF-gamma and tumor necrosis factor-alpha co-expression and expression of IL-7 receptor by melanoma antigen-specific CTL which were diminished by Treg. |
| 349 | 19651643 | PD1 blockade reverses the suppression of melanoma antigen-specific CTL by CD4+ CD25(Hi) regulatory T cells. |
| 350 | 19651643 | Regulatory CD4(+)CD25(Hi) T cells (Treg) and programmed death-1 (PD-1) molecule have emerged as pivotal players in immune regulation. |
| 351 | 19651643 | We identified Treg in the circulation of vaccinated melanoma patients and detected PD-1 expression on vaccine-induced melanoma antigen-specific CTLs, as well as on and within Treg from patients' peripheral blood. |
| 352 | 19651643 | PD-1 blockade promoted the generation of melanoma antigen-specific CTLs and masked their inhibition by Treg. |
| 353 | 19651643 | The mechanisms by which PD-1 blockade mediated immune enhancement included direct augmentation of melanoma antigen-specific CTL proliferation, heightening their resistance to inhibition by Treg and direct limitation of the inhibitory ability of Treg. |
| 354 | 19651643 | PD-1 blockade reversed the increased expression of PD-1 and PD-L1 on melanoma antigen-specific CTL by Treg, rescued INF-gamma and IL-2 or INF-gamma and tumor necrosis factor-alpha co-expression and expression of IL-7 receptor by melanoma antigen-specific CTL which were diminished by Treg. |
| 355 | 19830730 | In the current study, we profiled the early activation of CD8+ T cells by MHC class I-restricted peptide immunization to better understand the biology of this response. |
| 356 | 19830730 | Interestingly, CpG treatment modulated T-cell expression of the surface receptors PD-1 and CD25, providing insight into its possible adjuvant mechanism. |
| 357 | 20038811 | BTLA mediates inhibition of human tumor-specific CD8+ T cells that can be partially reversed by vaccination. |
| 358 | 20038811 | The function of antigen-specific CD8+ T cells, which may protect against both infectious and malignant diseases, can be impaired by ligation of their inhibitory receptors, which include CTL-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1). |
| 359 | 20038811 | Recently, B and T lymphocyte attenuator (BTLA) was identified as a novel inhibitory receptor with structural and functional similarities to CTLA-4 and PD-1. |
| 360 | 20038811 | Here we have demonstrated that as human viral antigen-specific CD8+ T cells differentiated from naive to effector cells, their surface expression of BTLA was gradually downregulated. |
| 361 | 20038811 | In marked contrast, human melanoma tumor antigen-specific effector CD8+ T cells persistently expressed high levels of BTLA in vivo and remained susceptible to functional inhibition by its ligand herpes virus entry mediator (HVEM). |
| 362 | 20038811 | Such persistence of BTLA expression was also found in tumor antigen-specific CD8+ T cells from melanoma patients with spontaneous antitumor immune responses and after conventional peptide vaccination. |
| 363 | 20038811 | Thus, BTLA activation inhibits the function of human CD8+ cancer-specific T cells, and appropriate immunotherapy may partially overcome this inhibition. |
| 364 | 20038811 | BTLA mediates inhibition of human tumor-specific CD8+ T cells that can be partially reversed by vaccination. |
| 365 | 20038811 | The function of antigen-specific CD8+ T cells, which may protect against both infectious and malignant diseases, can be impaired by ligation of their inhibitory receptors, which include CTL-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1). |
| 366 | 20038811 | Recently, B and T lymphocyte attenuator (BTLA) was identified as a novel inhibitory receptor with structural and functional similarities to CTLA-4 and PD-1. |
| 367 | 20038811 | Here we have demonstrated that as human viral antigen-specific CD8+ T cells differentiated from naive to effector cells, their surface expression of BTLA was gradually downregulated. |
| 368 | 20038811 | In marked contrast, human melanoma tumor antigen-specific effector CD8+ T cells persistently expressed high levels of BTLA in vivo and remained susceptible to functional inhibition by its ligand herpes virus entry mediator (HVEM). |
| 369 | 20038811 | Such persistence of BTLA expression was also found in tumor antigen-specific CD8+ T cells from melanoma patients with spontaneous antitumor immune responses and after conventional peptide vaccination. |
| 370 | 20038811 | Thus, BTLA activation inhibits the function of human CD8+ cancer-specific T cells, and appropriate immunotherapy may partially overcome this inhibition. |
| 371 | 20070620 | We longitudinally monitored the negative immune modulator programmed death (PD)-1 receptor on both CD4 and CD8 T cells, co-expressing the CD137 surface marker of recent activation, in a liver transplant cohort. |
| 372 | 20070620 | Liver recipients who progressed to CMV disease expressed elevated levels of PD-1 on CD137(+) CD4 and CD8 T cells, following stimulation with either full-length peptide libraries or CMV lysate. |
| 373 | 20070620 | CMV-specific T cells were still functional when both PD-1 and IL-10 were upregulated; however they showed a marked proliferation deficit, which may limit their ability to contain viremia and lead to CMV disease. |
| 374 | 20070620 | Our preliminary observations support further investigation of dual monitoring of PD-1 and IL-10, as potential immune markers of CMV disease. |
| 375 | 20070620 | We longitudinally monitored the negative immune modulator programmed death (PD)-1 receptor on both CD4 and CD8 T cells, co-expressing the CD137 surface marker of recent activation, in a liver transplant cohort. |
| 376 | 20070620 | Liver recipients who progressed to CMV disease expressed elevated levels of PD-1 on CD137(+) CD4 and CD8 T cells, following stimulation with either full-length peptide libraries or CMV lysate. |
| 377 | 20070620 | CMV-specific T cells were still functional when both PD-1 and IL-10 were upregulated; however they showed a marked proliferation deficit, which may limit their ability to contain viremia and lead to CMV disease. |
| 378 | 20070620 | Our preliminary observations support further investigation of dual monitoring of PD-1 and IL-10, as potential immune markers of CMV disease. |
| 379 | 20070620 | We longitudinally monitored the negative immune modulator programmed death (PD)-1 receptor on both CD4 and CD8 T cells, co-expressing the CD137 surface marker of recent activation, in a liver transplant cohort. |
| 380 | 20070620 | Liver recipients who progressed to CMV disease expressed elevated levels of PD-1 on CD137(+) CD4 and CD8 T cells, following stimulation with either full-length peptide libraries or CMV lysate. |
| 381 | 20070620 | CMV-specific T cells were still functional when both PD-1 and IL-10 were upregulated; however they showed a marked proliferation deficit, which may limit their ability to contain viremia and lead to CMV disease. |
| 382 | 20070620 | Our preliminary observations support further investigation of dual monitoring of PD-1 and IL-10, as potential immune markers of CMV disease. |
| 383 | 20121696 | Two families of receptors, the CD28 family and the tumor necrosis factor receptor (TNFR) family, have been found to be major players in providing costimulation to CD8+ T cells. |
| 384 | 20121696 | Programmed death-1 (PD-1), another member of the CD28 family, may contribute to functional defects of helpless memory CD8+ T cells. |
| 385 | 20121696 | Members of the TNFR family, such as CD27, 4-1BB, CD40, TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), and OX40, have also been implicated in the survival, generation, maintenance, and quality of virus-specific memory CD8+T cells. |
| 386 | 20121696 | The delivery of costimulatory molecules such as CD28, 4-1BB, and OX40 can help boost the generation and function of virus-specific memory CD8+ T cells. |
| 387 | 20160101 | PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. |
| 388 | 20160101 | Vaccination with irradiated B16 melanoma cells expressing either GM-CSF (Gvax) or Flt3-ligand (Fvax) combined with antibody blockade of the negative T-cell costimulatory receptor cytotoxic T-lymphocyte antigen-4 (CTLA-4) promotes rejection of preimplanted tumors. |
| 389 | 20160101 | Despite CTLA-4 blockade, T-cell proliferation and cytokine production can be inhibited by the interaction of programmed death-1 (PD-1) with its ligands PD-L1 and PD-L2 or by the interaction of PD-L1 with B7-1. |
| 390 | 20160101 | Here, we show that the combination of CTLA-4 and PD-1 blockade is more than twice as effective as either alone in promoting the rejection of B16 melanomas in conjunction with Fvax. |
| 391 | 20160101 | Combination PD-1 and CTLA-4 blockade increases effector T-cell (Teff) infiltration, resulting in highly advantageous Teff-to-regulatory T-cell ratios with the tumor. |
| 392 | 20160101 | The fraction of tumor-infiltrating Teffs expressing CTLA-4 and PD-1 increases, reflecting the proliferation and accumulation of cells that would otherwise be anergized. |
| 393 | 20160101 | IFN-gamma production increases in both the tumor and vaccine draining lymph nodes, as does the frequency of IFN-gamma/TNF-alpha double-producing CD8(+) T cells within the tumor. |
| 394 | 20160101 | These results suggest that combination blockade of the PD-1/PD-L1- and CTLA-4-negative costimulatory pathways allows tumor-specific T cells that would otherwise be inactivated to continue to expand and carry out effector functions, thereby shifting the tumor microenvironment from suppressive to inflammatory. |
| 395 | 20160101 | PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. |
| 396 | 20160101 | Vaccination with irradiated B16 melanoma cells expressing either GM-CSF (Gvax) or Flt3-ligand (Fvax) combined with antibody blockade of the negative T-cell costimulatory receptor cytotoxic T-lymphocyte antigen-4 (CTLA-4) promotes rejection of preimplanted tumors. |
| 397 | 20160101 | Despite CTLA-4 blockade, T-cell proliferation and cytokine production can be inhibited by the interaction of programmed death-1 (PD-1) with its ligands PD-L1 and PD-L2 or by the interaction of PD-L1 with B7-1. |
| 398 | 20160101 | Here, we show that the combination of CTLA-4 and PD-1 blockade is more than twice as effective as either alone in promoting the rejection of B16 melanomas in conjunction with Fvax. |
| 399 | 20160101 | Combination PD-1 and CTLA-4 blockade increases effector T-cell (Teff) infiltration, resulting in highly advantageous Teff-to-regulatory T-cell ratios with the tumor. |
| 400 | 20160101 | The fraction of tumor-infiltrating Teffs expressing CTLA-4 and PD-1 increases, reflecting the proliferation and accumulation of cells that would otherwise be anergized. |
| 401 | 20160101 | IFN-gamma production increases in both the tumor and vaccine draining lymph nodes, as does the frequency of IFN-gamma/TNF-alpha double-producing CD8(+) T cells within the tumor. |
| 402 | 20160101 | These results suggest that combination blockade of the PD-1/PD-L1- and CTLA-4-negative costimulatory pathways allows tumor-specific T cells that would otherwise be inactivated to continue to expand and carry out effector functions, thereby shifting the tumor microenvironment from suppressive to inflammatory. |
| 403 | 20160101 | PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. |
| 404 | 20160101 | Vaccination with irradiated B16 melanoma cells expressing either GM-CSF (Gvax) or Flt3-ligand (Fvax) combined with antibody blockade of the negative T-cell costimulatory receptor cytotoxic T-lymphocyte antigen-4 (CTLA-4) promotes rejection of preimplanted tumors. |
| 405 | 20160101 | Despite CTLA-4 blockade, T-cell proliferation and cytokine production can be inhibited by the interaction of programmed death-1 (PD-1) with its ligands PD-L1 and PD-L2 or by the interaction of PD-L1 with B7-1. |
| 406 | 20160101 | Here, we show that the combination of CTLA-4 and PD-1 blockade is more than twice as effective as either alone in promoting the rejection of B16 melanomas in conjunction with Fvax. |
| 407 | 20160101 | Combination PD-1 and CTLA-4 blockade increases effector T-cell (Teff) infiltration, resulting in highly advantageous Teff-to-regulatory T-cell ratios with the tumor. |
| 408 | 20160101 | The fraction of tumor-infiltrating Teffs expressing CTLA-4 and PD-1 increases, reflecting the proliferation and accumulation of cells that would otherwise be anergized. |
| 409 | 20160101 | IFN-gamma production increases in both the tumor and vaccine draining lymph nodes, as does the frequency of IFN-gamma/TNF-alpha double-producing CD8(+) T cells within the tumor. |
| 410 | 20160101 | These results suggest that combination blockade of the PD-1/PD-L1- and CTLA-4-negative costimulatory pathways allows tumor-specific T cells that would otherwise be inactivated to continue to expand and carry out effector functions, thereby shifting the tumor microenvironment from suppressive to inflammatory. |
| 411 | 20160101 | PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. |
| 412 | 20160101 | Vaccination with irradiated B16 melanoma cells expressing either GM-CSF (Gvax) or Flt3-ligand (Fvax) combined with antibody blockade of the negative T-cell costimulatory receptor cytotoxic T-lymphocyte antigen-4 (CTLA-4) promotes rejection of preimplanted tumors. |
| 413 | 20160101 | Despite CTLA-4 blockade, T-cell proliferation and cytokine production can be inhibited by the interaction of programmed death-1 (PD-1) with its ligands PD-L1 and PD-L2 or by the interaction of PD-L1 with B7-1. |
| 414 | 20160101 | Here, we show that the combination of CTLA-4 and PD-1 blockade is more than twice as effective as either alone in promoting the rejection of B16 melanomas in conjunction with Fvax. |
| 415 | 20160101 | Combination PD-1 and CTLA-4 blockade increases effector T-cell (Teff) infiltration, resulting in highly advantageous Teff-to-regulatory T-cell ratios with the tumor. |
| 416 | 20160101 | The fraction of tumor-infiltrating Teffs expressing CTLA-4 and PD-1 increases, reflecting the proliferation and accumulation of cells that would otherwise be anergized. |
| 417 | 20160101 | IFN-gamma production increases in both the tumor and vaccine draining lymph nodes, as does the frequency of IFN-gamma/TNF-alpha double-producing CD8(+) T cells within the tumor. |
| 418 | 20160101 | These results suggest that combination blockade of the PD-1/PD-L1- and CTLA-4-negative costimulatory pathways allows tumor-specific T cells that would otherwise be inactivated to continue to expand and carry out effector functions, thereby shifting the tumor microenvironment from suppressive to inflammatory. |
| 419 | 20160101 | PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. |
| 420 | 20160101 | Vaccination with irradiated B16 melanoma cells expressing either GM-CSF (Gvax) or Flt3-ligand (Fvax) combined with antibody blockade of the negative T-cell costimulatory receptor cytotoxic T-lymphocyte antigen-4 (CTLA-4) promotes rejection of preimplanted tumors. |
| 421 | 20160101 | Despite CTLA-4 blockade, T-cell proliferation and cytokine production can be inhibited by the interaction of programmed death-1 (PD-1) with its ligands PD-L1 and PD-L2 or by the interaction of PD-L1 with B7-1. |
| 422 | 20160101 | Here, we show that the combination of CTLA-4 and PD-1 blockade is more than twice as effective as either alone in promoting the rejection of B16 melanomas in conjunction with Fvax. |
| 423 | 20160101 | Combination PD-1 and CTLA-4 blockade increases effector T-cell (Teff) infiltration, resulting in highly advantageous Teff-to-regulatory T-cell ratios with the tumor. |
| 424 | 20160101 | The fraction of tumor-infiltrating Teffs expressing CTLA-4 and PD-1 increases, reflecting the proliferation and accumulation of cells that would otherwise be anergized. |
| 425 | 20160101 | IFN-gamma production increases in both the tumor and vaccine draining lymph nodes, as does the frequency of IFN-gamma/TNF-alpha double-producing CD8(+) T cells within the tumor. |
| 426 | 20160101 | These results suggest that combination blockade of the PD-1/PD-L1- and CTLA-4-negative costimulatory pathways allows tumor-specific T cells that would otherwise be inactivated to continue to expand and carry out effector functions, thereby shifting the tumor microenvironment from suppressive to inflammatory. |
| 427 | 20392496 | IL-4 directs both CD4 and CD8 T cells to produce Th2 cytokines in vitro, but only CD4 T cells produce these cytokines in response to alum-precipitated protein in vivo. |
| 428 | 20392496 | While IL-4 directs CD4 T cells to produce Th2 cytokines (including IL-4, IL-13, IL-5) in vitro it has been shown that production of these cytokines can be induced in vivo in the absence of IL-4/IL-13/STAT-6 signaling. |
| 429 | 20392496 | The present report shows that CD8 as well as CD4 T cells activated through their TCR, in vitro upregulate the Th2-features - IL-4, IL-13, IL-5, and GATA-3. |
| 430 | 20392496 | However, in vivo while alum-precipitated antigen strongly and selectively induces these Th2-features in CD4 T cells, CD8 T cells mount a markedly different response to this antigen. |
| 431 | 20392496 | This CD8 response is associated with strong proliferation and production of IFN-gamma, but no Th2-features are induced. |
| 432 | 20392496 | Alum-protein formulations are widely used in human vaccines and typically induce strong antibody responses characterized by the differentiation of IL-4-producing CD4 T cells and immunoglobulin class switching to IgG1. |
| 433 | 20392496 | Analysis of the in vivo response to alum-precipitated protein shows that while subsets of CD4 T cells strongly upregulate Th2 and follicular helper T cell features including the surface markers OX40, CXCR5, PD-1, IL-17RB and the transcription factor c-Maf, CD8 T cells do not. |
| 434 | 20392496 | These discrete differences between responding CD4 and CD8 T cells provide further insight into the differences between Th2 polarization of CD4 T cells directed by IL-4 in vitro and the induction of IL-4 production by CD4 T cells in vivo in response to alum-precipitated protein. |
| 435 | 20445343 | Enhanced tumor eradication by combining CTLA-4 or PD-1 blockade with CpG therapy. |
| 436 | 20445343 | Previous reports demonstrate that cytotoxic T lymphocyte antigen-4 (CTLA-4)-blocking antibodies promote T-cell activation and render T effector cells resistant to T regulatory cells (Tregs) whereas programmed death receptor-1 (PD-1)/PD-L1 blockade results in loss of peripheral tolerance. |
| 437 | 20445343 | Herein, we explored single or combined antibody blockade of CTLA-4 and PD-1 alone or combined with the toll-like receptor agonists CpG or bacillus Calmette-Guérin for treatment of murine experimental bladder cancer. |
| 438 | 20445343 | However, elevated levels of circulating CD107a expressing CD8 T cells were found in the aCTLA-4 plus aPD-1 group. |
| 439 | 20445343 | CpG plus aCTLA-4 or aPD-1 increased the numbers of circulating tumor-specific CD107a expressing CD8 T cells as well as activated (CD25FoxP3-) CD4 splenocytes. |
| 440 | 20445343 | Thus, the combination of CpG with CTLA-4 or PD-1 blockade improved long-term survival and led to increased levels of tumor-reactive T cells and reduced numbers of Tregs at the tumor site. |
| 441 | 20445343 | Enhanced tumor eradication by combining CTLA-4 or PD-1 blockade with CpG therapy. |
| 442 | 20445343 | Previous reports demonstrate that cytotoxic T lymphocyte antigen-4 (CTLA-4)-blocking antibodies promote T-cell activation and render T effector cells resistant to T regulatory cells (Tregs) whereas programmed death receptor-1 (PD-1)/PD-L1 blockade results in loss of peripheral tolerance. |
| 443 | 20445343 | Herein, we explored single or combined antibody blockade of CTLA-4 and PD-1 alone or combined with the toll-like receptor agonists CpG or bacillus Calmette-Guérin for treatment of murine experimental bladder cancer. |
| 444 | 20445343 | However, elevated levels of circulating CD107a expressing CD8 T cells were found in the aCTLA-4 plus aPD-1 group. |
| 445 | 20445343 | CpG plus aCTLA-4 or aPD-1 increased the numbers of circulating tumor-specific CD107a expressing CD8 T cells as well as activated (CD25FoxP3-) CD4 splenocytes. |
| 446 | 20445343 | Thus, the combination of CpG with CTLA-4 or PD-1 blockade improved long-term survival and led to increased levels of tumor-reactive T cells and reduced numbers of Tregs at the tumor site. |
| 447 | 20445343 | Enhanced tumor eradication by combining CTLA-4 or PD-1 blockade with CpG therapy. |
| 448 | 20445343 | Previous reports demonstrate that cytotoxic T lymphocyte antigen-4 (CTLA-4)-blocking antibodies promote T-cell activation and render T effector cells resistant to T regulatory cells (Tregs) whereas programmed death receptor-1 (PD-1)/PD-L1 blockade results in loss of peripheral tolerance. |
| 449 | 20445343 | Herein, we explored single or combined antibody blockade of CTLA-4 and PD-1 alone or combined with the toll-like receptor agonists CpG or bacillus Calmette-Guérin for treatment of murine experimental bladder cancer. |
| 450 | 20445343 | However, elevated levels of circulating CD107a expressing CD8 T cells were found in the aCTLA-4 plus aPD-1 group. |
| 451 | 20445343 | CpG plus aCTLA-4 or aPD-1 increased the numbers of circulating tumor-specific CD107a expressing CD8 T cells as well as activated (CD25FoxP3-) CD4 splenocytes. |
| 452 | 20445343 | Thus, the combination of CpG with CTLA-4 or PD-1 blockade improved long-term survival and led to increased levels of tumor-reactive T cells and reduced numbers of Tregs at the tumor site. |
| 453 | 20445343 | Enhanced tumor eradication by combining CTLA-4 or PD-1 blockade with CpG therapy. |
| 454 | 20445343 | Previous reports demonstrate that cytotoxic T lymphocyte antigen-4 (CTLA-4)-blocking antibodies promote T-cell activation and render T effector cells resistant to T regulatory cells (Tregs) whereas programmed death receptor-1 (PD-1)/PD-L1 blockade results in loss of peripheral tolerance. |
| 455 | 20445343 | Herein, we explored single or combined antibody blockade of CTLA-4 and PD-1 alone or combined with the toll-like receptor agonists CpG or bacillus Calmette-Guérin for treatment of murine experimental bladder cancer. |
| 456 | 20445343 | However, elevated levels of circulating CD107a expressing CD8 T cells were found in the aCTLA-4 plus aPD-1 group. |
| 457 | 20445343 | CpG plus aCTLA-4 or aPD-1 increased the numbers of circulating tumor-specific CD107a expressing CD8 T cells as well as activated (CD25FoxP3-) CD4 splenocytes. |
| 458 | 20445343 | Thus, the combination of CpG with CTLA-4 or PD-1 blockade improved long-term survival and led to increased levels of tumor-reactive T cells and reduced numbers of Tregs at the tumor site. |
| 459 | 20480224 | CD4+ T cells inhibit the neu-specific CD8+ T-cell exhaustion during the priming phase of immune responses against breast cancer. |
| 460 | 20480224 | Studies conducted in animal model of infectious diseases or H-Y antigen model suggest a crucial role for CD4+ T cells in providing help for CD8+ T-cell memory responses. |
| 461 | 20480224 | Although this concept has been applied to cancer vaccine design, the role of CD4+ T cells in the memory differentiation of CD8+ T cells and retention of their anti-tumor function have never been tested in breast cancer model. |
| 462 | 20480224 | Such differential effects, in vivo, were associated with higher frequency of CD8+PD-L1+ and CD8+PD-1+ T cells in animals harboring helpless T cells as well as higher titer of IL-2 in the sera of animals harboring helped T cells. |
| 463 | 20480224 | However, depletion of CD4+ T cells did not alter the ability of neu-specific CD8+ T cells to differentiate into memory cells and to retain their effector function against the tumor during recall challenge. |
| 464 | 20480224 | These results suggest the inhibitory role of CD4+ T cells on CD8+ T-cell exhaustion without substantial effects on the differentiation of memory T cells during priming phase of the immune responses against breast cancer. |
| 465 | 20551512 | The inhibitory receptor programmed death 1 (PD-1) is upregulated on antigen-specific CD8+ T cells during persistent viral infections. |
| 466 | 20551512 | Interaction with PD-1 ligand 1 (PD-L1) contributes to functional exhaustion of responding T cells and may limit immunopathology during infection. |
| 467 | 20551512 | We found that PD-L1 expression on hematopoietic cells inhibited CD8+ T cell numbers and function after LCMV CL-13 infection. |
| 468 | 20551512 | Together, these data demonstrate that there are distinct roles for PD-L1 on hematopoietic and nonhematopoietic cells in regulating CD8+ T cell responses and viral clearance during chronic viral infection. |
| 469 | 20551512 | The inhibitory receptor programmed death 1 (PD-1) is upregulated on antigen-specific CD8+ T cells during persistent viral infections. |
| 470 | 20551512 | Interaction with PD-1 ligand 1 (PD-L1) contributes to functional exhaustion of responding T cells and may limit immunopathology during infection. |
| 471 | 20551512 | We found that PD-L1 expression on hematopoietic cells inhibited CD8+ T cell numbers and function after LCMV CL-13 infection. |
| 472 | 20551512 | Together, these data demonstrate that there are distinct roles for PD-L1 on hematopoietic and nonhematopoietic cells in regulating CD8+ T cell responses and viral clearance during chronic viral infection. |
| 473 | 20725863 | The P38 and ERK Mitogen-Activated Protein Kinase (MAPK) pathways govern the regulation of cytokines (IL-2, IL-10, and TNF-α) as well biomarkers (PD-1, Fas/FasL, among others) that are skewed in chronic HIV infection. |
| 474 | 20725863 | HIV utilizes the P38 and ERK pathways to produce new virions and to deplete CD4+ T cells from the host's immune system. |
| 475 | 21039472 | Phenotypic and functional profiling of malaria-induced CD8 and CD4 T cells during blood-stage infection with Plasmodium yoelii. |
| 476 | 21039472 | It is widely accepted that antibodies and CD4 T cells play critical roles in the immune response during the blood stage of malaria, whereas the role of CD8 T cells remains controversial. |
| 477 | 21039472 | Here, we show that both CD8 and CD4 T cells robustly responded to an acute self-limiting blood-stage infection with Plasmodium yoelii. |
| 478 | 21039472 | Similar to antigen-specific T cells, both CD8 and CD4 T cells showed dynamic expression of the surface proteins interleukin (IL)-7R and programmed death-1 (PD-1). |
| 479 | 21039472 | Additionally, activated CD8 T cells showed differences in the expression of Killer cell lectin-like receptor G1, L-selectin and B cell lymphoma-2 and produced granzyme B, indicating cytotoxic activity, and the initially high expression of T-box transcription factor TBX21 in malaria-activated CD4 T cells indicated an early T helper type 1 (Th1)-skewed immune response. |
| 480 | 21039472 | Our data demonstrate that blood-stage malaria infection results in a striking T-cell response and that activated CD8 and CD4 T cells have phenotypic and functional characteristics that are consistent with conventional antigen-specific effector and memory T cells. |
| 481 | 21039472 | Therefore, a better understanding of the CD8 and CD4 T-cell response induced by blood-stage infection may prove to be essential in the development of a vaccine that targets the erythrocytic stage of the malarial parasite. |
| 482 | 21061197 | Programmed cell death-1 (PD-1) is a member of the CD28 superfamily that delivers negative signals upon interaction with its two ligands, PD-L1 or PD-L2. |
| 483 | 21061197 | PD-1 and its ligands are broadly expressed and exert a wider range of immunoregulatory roles in T cells activation and tolerance compared with other CD28 members. |
| 484 | 21061197 | Programmed cell death-1 (PD-1) is a member of the CD28 superfamily that delivers negative signals upon interaction with its two ligands, PD-L1 or PD-L2. |
| 485 | 21061197 | PD-1 and its ligands are broadly expressed and exert a wider range of immunoregulatory roles in T cells activation and tolerance compared with other CD28 members. |
| 486 | 21074057 | Immune checkpoint proteins: a new therapeutic paradigm for cancer--preclinical background: CTLA-4 and PD-1 blockade. |
| 487 | 21074057 | Promising clinical data have already been generated in melanoma and other tumor types with human antibodies directed against cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed death-1 (PD-1). |
| 488 | 21074057 | In contrast, much of the early work with anti-CTLA-4 antibodies indicated that it had a potent therapeutic effect only when combined with granulocyte-macrophage colony-stimulating factor (GM-CSF)-transduced tumor vaccines, and that the antibody alone was effective only in the most immunogenic tumor models in mice. |
| 489 | 21074057 | Murine experiments also suggested that CTLA-4 abrogation might function via important effects on natural T-regulatory cells that were CD4(+), CD25(+high), and FOXp3(+), but this has not been borne out in experiments using peripheral blood mononuclear cells from patients treated with anti-CTLA-4 antibodies, and unlike in animals, in humans the exact mechanism(s) by which CTLA-4 abrogation induced an anti-tumor effect is still unclear. |
| 490 | 21074057 | Abrogation of PD-1 functions via different immune signaling pathways than CTLA-4 and is likely to have a different spectrum of effects than blocking CTLA-4. |
| 491 | 21074057 | Immune checkpoint proteins: a new therapeutic paradigm for cancer--preclinical background: CTLA-4 and PD-1 blockade. |
| 492 | 21074057 | Promising clinical data have already been generated in melanoma and other tumor types with human antibodies directed against cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed death-1 (PD-1). |
| 493 | 21074057 | In contrast, much of the early work with anti-CTLA-4 antibodies indicated that it had a potent therapeutic effect only when combined with granulocyte-macrophage colony-stimulating factor (GM-CSF)-transduced tumor vaccines, and that the antibody alone was effective only in the most immunogenic tumor models in mice. |
| 494 | 21074057 | Murine experiments also suggested that CTLA-4 abrogation might function via important effects on natural T-regulatory cells that were CD4(+), CD25(+high), and FOXp3(+), but this has not been borne out in experiments using peripheral blood mononuclear cells from patients treated with anti-CTLA-4 antibodies, and unlike in animals, in humans the exact mechanism(s) by which CTLA-4 abrogation induced an anti-tumor effect is still unclear. |
| 495 | 21074057 | Abrogation of PD-1 functions via different immune signaling pathways than CTLA-4 and is likely to have a different spectrum of effects than blocking CTLA-4. |
| 496 | 21074057 | Immune checkpoint proteins: a new therapeutic paradigm for cancer--preclinical background: CTLA-4 and PD-1 blockade. |
| 497 | 21074057 | Promising clinical data have already been generated in melanoma and other tumor types with human antibodies directed against cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed death-1 (PD-1). |
| 498 | 21074057 | In contrast, much of the early work with anti-CTLA-4 antibodies indicated that it had a potent therapeutic effect only when combined with granulocyte-macrophage colony-stimulating factor (GM-CSF)-transduced tumor vaccines, and that the antibody alone was effective only in the most immunogenic tumor models in mice. |
| 499 | 21074057 | Murine experiments also suggested that CTLA-4 abrogation might function via important effects on natural T-regulatory cells that were CD4(+), CD25(+high), and FOXp3(+), but this has not been borne out in experiments using peripheral blood mononuclear cells from patients treated with anti-CTLA-4 antibodies, and unlike in animals, in humans the exact mechanism(s) by which CTLA-4 abrogation induced an anti-tumor effect is still unclear. |
| 500 | 21074057 | Abrogation of PD-1 functions via different immune signaling pathways than CTLA-4 and is likely to have a different spectrum of effects than blocking CTLA-4. |
| 501 | 21147929 | CD8(+) cells from the vHIV individuals exhibited the highest HIV-suppressing activity and had elevated frequencies of CD45RA(-) CD27(+) and PD-1(+) (CD279(+)) cells. |
| 502 | 21147929 | Functional assessments of CD8(+) cells sorted into distinct subsets established that maximal CNAR activity was mediated by CD45RA(-) CCR7(-) CD27(+) and PD-1(+) CD8(+) cells. |
| 503 | 21147929 | Together, these studies suggest that CNAR is driven by HIV replication and that this antiviral activity is associated with oligoclonally expanded activated CD8(+) cells expressing PD-1 and having a transitional memory cell phenotype. |
| 504 | 21147929 | CD8(+) cells from the vHIV individuals exhibited the highest HIV-suppressing activity and had elevated frequencies of CD45RA(-) CD27(+) and PD-1(+) (CD279(+)) cells. |
| 505 | 21147929 | Functional assessments of CD8(+) cells sorted into distinct subsets established that maximal CNAR activity was mediated by CD45RA(-) CCR7(-) CD27(+) and PD-1(+) CD8(+) cells. |
| 506 | 21147929 | Together, these studies suggest that CNAR is driven by HIV replication and that this antiviral activity is associated with oligoclonally expanded activated CD8(+) cells expressing PD-1 and having a transitional memory cell phenotype. |
| 507 | 21147929 | CD8(+) cells from the vHIV individuals exhibited the highest HIV-suppressing activity and had elevated frequencies of CD45RA(-) CD27(+) and PD-1(+) (CD279(+)) cells. |
| 508 | 21147929 | Functional assessments of CD8(+) cells sorted into distinct subsets established that maximal CNAR activity was mediated by CD45RA(-) CCR7(-) CD27(+) and PD-1(+) CD8(+) cells. |
| 509 | 21147929 | Together, these studies suggest that CNAR is driven by HIV replication and that this antiviral activity is associated with oligoclonally expanded activated CD8(+) cells expressing PD-1 and having a transitional memory cell phenotype. |
| 510 | 21240487 | Various studies have shown that positive costimulatory pathways such as the CD28 and CD40 pathways can influence the expansion and cytokine production by iNKT cells. |
| 511 | 21240487 | To study whether PD-L1 deficiency on NKT cells would enhance antigen-specific T-cell responses, we utilized CD8(+) OT-1 OVA transgenic T cells. α-GalCer enhanced the expansion and cytokine production of OT-1 CD8(+) cells after adoptive transfer into wild-type recipients. |
| 512 | 21240487 | However, this expansion was significantly enhanced when OT-1 CD8(+) T cells were adoptively transferred into PD-L1(-/-) recipients. |
| 513 | 21240487 | PD-L1(-/-) mice given dendritic cells loaded with antigen and α-GalCer had a significant reduction in tumor growth and this was associated with increased trafficking of antigen-presenting cells and CD8(+) T cells to the tumors. |
| 514 | 21240487 | These data demonstrate that abrogating PDL1:PD-1 interactions during the activation of iNKT cells amplifies an anti-tumor response when coupled with DC vaccination. |
| 515 | 21314428 | Distinguishing features of T(FH) cells are the expression of CXCR5, PD-1, SAP (SH2D1A), IL-21, and ICOS, among other molecules, and the absence of Blimp-1 (prdm1). |
| 516 | 21376795 | Impaired hepatitis B vaccine responses during chronic hepatitis C infection: involvement of the PD-1 pathway in regulating CD4(+) T cell responses. |
| 517 | 21376795 | In this report, we further investigated the role of the PD-1 pathway in regulation of CD4(+) T cell responses to HBV vaccination in HCV-infected individuals. |
| 518 | 21376795 | CD4(+) T cell responses to ex vivo stimulations of anti-CD3/CD28 antibodies or hepatitis B surface antigen (HBsAg) were found to be lower in HBV vaccine non-responders compared to those responders in HCV-infected individuals who had received a series of HBV immunizations. |
| 519 | 21376795 | PD-1 expression on CD4(+) T cells was detected at relatively higher levels in these HBV vaccine non-responders than those who responded, and this was inversely associated with the cell activation status. |
| 520 | 21376795 | Importantly, blocking the PD-1 pathway improved T cell activation and proliferation in response to ex vivo HBsAg or anti-CD3/CD28 stimulation in HBV vaccine non-responders. |
| 521 | 21376795 | These results suggest that PD-1 signaling may be involved in impairing CD4(+) T cell responses to HBV vaccination in subjects with HCV infection, and raise the possibility that blocking this negative signaling pathway might improve success rates of immunization in the setting of chronic viral infection. |
| 522 | 21376795 | Impaired hepatitis B vaccine responses during chronic hepatitis C infection: involvement of the PD-1 pathway in regulating CD4(+) T cell responses. |
| 523 | 21376795 | In this report, we further investigated the role of the PD-1 pathway in regulation of CD4(+) T cell responses to HBV vaccination in HCV-infected individuals. |
| 524 | 21376795 | CD4(+) T cell responses to ex vivo stimulations of anti-CD3/CD28 antibodies or hepatitis B surface antigen (HBsAg) were found to be lower in HBV vaccine non-responders compared to those responders in HCV-infected individuals who had received a series of HBV immunizations. |
| 525 | 21376795 | PD-1 expression on CD4(+) T cells was detected at relatively higher levels in these HBV vaccine non-responders than those who responded, and this was inversely associated with the cell activation status. |
| 526 | 21376795 | Importantly, blocking the PD-1 pathway improved T cell activation and proliferation in response to ex vivo HBsAg or anti-CD3/CD28 stimulation in HBV vaccine non-responders. |
| 527 | 21376795 | These results suggest that PD-1 signaling may be involved in impairing CD4(+) T cell responses to HBV vaccination in subjects with HCV infection, and raise the possibility that blocking this negative signaling pathway might improve success rates of immunization in the setting of chronic viral infection. |
| 528 | 21376795 | Impaired hepatitis B vaccine responses during chronic hepatitis C infection: involvement of the PD-1 pathway in regulating CD4(+) T cell responses. |
| 529 | 21376795 | In this report, we further investigated the role of the PD-1 pathway in regulation of CD4(+) T cell responses to HBV vaccination in HCV-infected individuals. |
| 530 | 21376795 | CD4(+) T cell responses to ex vivo stimulations of anti-CD3/CD28 antibodies or hepatitis B surface antigen (HBsAg) were found to be lower in HBV vaccine non-responders compared to those responders in HCV-infected individuals who had received a series of HBV immunizations. |
| 531 | 21376795 | PD-1 expression on CD4(+) T cells was detected at relatively higher levels in these HBV vaccine non-responders than those who responded, and this was inversely associated with the cell activation status. |
| 532 | 21376795 | Importantly, blocking the PD-1 pathway improved T cell activation and proliferation in response to ex vivo HBsAg or anti-CD3/CD28 stimulation in HBV vaccine non-responders. |
| 533 | 21376795 | These results suggest that PD-1 signaling may be involved in impairing CD4(+) T cell responses to HBV vaccination in subjects with HCV infection, and raise the possibility that blocking this negative signaling pathway might improve success rates of immunization in the setting of chronic viral infection. |
| 534 | 21376795 | Impaired hepatitis B vaccine responses during chronic hepatitis C infection: involvement of the PD-1 pathway in regulating CD4(+) T cell responses. |
| 535 | 21376795 | In this report, we further investigated the role of the PD-1 pathway in regulation of CD4(+) T cell responses to HBV vaccination in HCV-infected individuals. |
| 536 | 21376795 | CD4(+) T cell responses to ex vivo stimulations of anti-CD3/CD28 antibodies or hepatitis B surface antigen (HBsAg) were found to be lower in HBV vaccine non-responders compared to those responders in HCV-infected individuals who had received a series of HBV immunizations. |
| 537 | 21376795 | PD-1 expression on CD4(+) T cells was detected at relatively higher levels in these HBV vaccine non-responders than those who responded, and this was inversely associated with the cell activation status. |
| 538 | 21376795 | Importantly, blocking the PD-1 pathway improved T cell activation and proliferation in response to ex vivo HBsAg or anti-CD3/CD28 stimulation in HBV vaccine non-responders. |
| 539 | 21376795 | These results suggest that PD-1 signaling may be involved in impairing CD4(+) T cell responses to HBV vaccination in subjects with HCV infection, and raise the possibility that blocking this negative signaling pathway might improve success rates of immunization in the setting of chronic viral infection. |
| 540 | 21376795 | Impaired hepatitis B vaccine responses during chronic hepatitis C infection: involvement of the PD-1 pathway in regulating CD4(+) T cell responses. |
| 541 | 21376795 | In this report, we further investigated the role of the PD-1 pathway in regulation of CD4(+) T cell responses to HBV vaccination in HCV-infected individuals. |
| 542 | 21376795 | CD4(+) T cell responses to ex vivo stimulations of anti-CD3/CD28 antibodies or hepatitis B surface antigen (HBsAg) were found to be lower in HBV vaccine non-responders compared to those responders in HCV-infected individuals who had received a series of HBV immunizations. |
| 543 | 21376795 | PD-1 expression on CD4(+) T cells was detected at relatively higher levels in these HBV vaccine non-responders than those who responded, and this was inversely associated with the cell activation status. |
| 544 | 21376795 | Importantly, blocking the PD-1 pathway improved T cell activation and proliferation in response to ex vivo HBsAg or anti-CD3/CD28 stimulation in HBV vaccine non-responders. |
| 545 | 21376795 | These results suggest that PD-1 signaling may be involved in impairing CD4(+) T cell responses to HBV vaccination in subjects with HCV infection, and raise the possibility that blocking this negative signaling pathway might improve success rates of immunization in the setting of chronic viral infection. |
| 546 | 21383243 | In this study, we provide a comprehensive description of phenotype, function, and gene expression profiles of PD-1(hi) versus PD-1(lo) CD8 T cells in the peripheral blood of healthy human adults as follows: 1) the percentage of naive and memory CD8 T cells varied widely in the peripheral blood cells of healthy humans, and PD-1 was expressed by the memory CD8 T cells; 2) PD-1(hi) CD8 T cells in healthy humans did not significantly correlate with the PD-1(hi) exhausted gene signature of HIV-specific human CD8 T cells or chronic lymphocytic choriomeningitis virus-specific CD8 T cells from mice; 3) PD-1 expression did not directly affect the ability of CD8 T cells to secrete cytokines in healthy adults; 4) PD-1 was expressed by the effector memory compared with terminally differentiated effector CD8 T cells; and 5) finally, an interesting inverse relationship between CD45RA and PD-1 expression was observed. |
| 547 | 21383243 | In conclusion, our study shows that most PD-1(hi) CD8 T cells in healthy adult humans are effector memory cells rather than exhausted cells. |
| 548 | 21383243 | In this study, we provide a comprehensive description of phenotype, function, and gene expression profiles of PD-1(hi) versus PD-1(lo) CD8 T cells in the peripheral blood of healthy human adults as follows: 1) the percentage of naive and memory CD8 T cells varied widely in the peripheral blood cells of healthy humans, and PD-1 was expressed by the memory CD8 T cells; 2) PD-1(hi) CD8 T cells in healthy humans did not significantly correlate with the PD-1(hi) exhausted gene signature of HIV-specific human CD8 T cells or chronic lymphocytic choriomeningitis virus-specific CD8 T cells from mice; 3) PD-1 expression did not directly affect the ability of CD8 T cells to secrete cytokines in healthy adults; 4) PD-1 was expressed by the effector memory compared with terminally differentiated effector CD8 T cells; and 5) finally, an interesting inverse relationship between CD45RA and PD-1 expression was observed. |
| 549 | 21383243 | In conclusion, our study shows that most PD-1(hi) CD8 T cells in healthy adult humans are effector memory cells rather than exhausted cells. |
| 550 | 21389868 | Enhancement of vaccine-induced primary and memory CD8(+) T-cell responses by soluble PD-1. |
| 551 | 21389868 | Programmed death 1 (PD-1) signaling through its ligands, PD-L1 and PD-L2, has been known to negatively regulate T-cell responses. |
| 552 | 21389868 | In this study, we evaluated the effects of soluble PD-1 (sPD-1) as a blockade of PD-1 and PD-L1 on vaccine-elicited antigen-specific T-cell responses in mice. |
| 553 | 21389868 | In addition, the frequency and functional activity of adoptively transferred OT-I cells, particularly memory CD8(+) T cells, were augmented by coadministration of sPD-1 DNA, which was closely associated with increased T-cell proliferation and reduced T-cell apoptosis through upregulation of Bcl-xL expression during T-cell activation. |
| 554 | 21389868 | Enhancement of vaccine-induced primary and memory CD8(+) T-cell responses by soluble PD-1. |
| 555 | 21389868 | Programmed death 1 (PD-1) signaling through its ligands, PD-L1 and PD-L2, has been known to negatively regulate T-cell responses. |
| 556 | 21389868 | In this study, we evaluated the effects of soluble PD-1 (sPD-1) as a blockade of PD-1 and PD-L1 on vaccine-elicited antigen-specific T-cell responses in mice. |
| 557 | 21389868 | In addition, the frequency and functional activity of adoptively transferred OT-I cells, particularly memory CD8(+) T cells, were augmented by coadministration of sPD-1 DNA, which was closely associated with increased T-cell proliferation and reduced T-cell apoptosis through upregulation of Bcl-xL expression during T-cell activation. |
| 558 | 21389868 | Enhancement of vaccine-induced primary and memory CD8(+) T-cell responses by soluble PD-1. |
| 559 | 21389868 | Programmed death 1 (PD-1) signaling through its ligands, PD-L1 and PD-L2, has been known to negatively regulate T-cell responses. |
| 560 | 21389868 | In this study, we evaluated the effects of soluble PD-1 (sPD-1) as a blockade of PD-1 and PD-L1 on vaccine-elicited antigen-specific T-cell responses in mice. |
| 561 | 21389868 | In addition, the frequency and functional activity of adoptively transferred OT-I cells, particularly memory CD8(+) T cells, were augmented by coadministration of sPD-1 DNA, which was closely associated with increased T-cell proliferation and reduced T-cell apoptosis through upregulation of Bcl-xL expression during T-cell activation. |
| 562 | 21419713 | Expansion of interferon-gamma-producing multifunctional CD4+ T-cells and dysfunctional CD8+ T-cells by glypican-3 peptide library in hepatocellular carcinoma patients. |
| 563 | 21419713 | Glypican-3 is a promising target for immunotherapy for hepatocellular carcinoma, but limited data exist regarding its immunogenicity in patients with diverse HLA types, immunogenicity for CD4(+) T-cells, and the impact of inhibitory co-stimulation on glypican-3-specific T-cells. |
| 564 | 21419713 | Using a 15mer overlapping peptide library for glypican-3, PBMC from patients with HCC were assessed ex vivo and after short-term in vitro expansion for tumor antigen-specific T-cell responses with and without blockade of PD-1/PD-L1 and CTLA-4 signaling. |
| 565 | 21419713 | Glypican-3-specific T-cells were undetectable ex vivo, but primarily IFNγ(+)TNFα(+) CD4(+) T-cells expanded with short-term in vitro stimulation in 10/19 (52%) patients. |
| 566 | 21419713 | Glypican-3-specific CD8(+) T-cells predominantly produced TNFα, but did not secrete IFNγ nor degranulate. |
| 567 | 21419713 | CTLA-4 and PD-1 blockade minimally impacted the cytokine secretion and proliferation of glypican-3-specific T-cells. |
| 568 | 21419713 | These data suggest that CD8(+) T-cell-directed tumor vaccines in HCC may have limited potential for efficacy unless optimal co-stimulation conditions can be identified but CD4(+)-directed vaccines merit consideration. |
| 569 | 21419713 | Expansion of interferon-gamma-producing multifunctional CD4+ T-cells and dysfunctional CD8+ T-cells by glypican-3 peptide library in hepatocellular carcinoma patients. |
| 570 | 21419713 | Glypican-3 is a promising target for immunotherapy for hepatocellular carcinoma, but limited data exist regarding its immunogenicity in patients with diverse HLA types, immunogenicity for CD4(+) T-cells, and the impact of inhibitory co-stimulation on glypican-3-specific T-cells. |
| 571 | 21419713 | Using a 15mer overlapping peptide library for glypican-3, PBMC from patients with HCC were assessed ex vivo and after short-term in vitro expansion for tumor antigen-specific T-cell responses with and without blockade of PD-1/PD-L1 and CTLA-4 signaling. |
| 572 | 21419713 | Glypican-3-specific T-cells were undetectable ex vivo, but primarily IFNγ(+)TNFα(+) CD4(+) T-cells expanded with short-term in vitro stimulation in 10/19 (52%) patients. |
| 573 | 21419713 | Glypican-3-specific CD8(+) T-cells predominantly produced TNFα, but did not secrete IFNγ nor degranulate. |
| 574 | 21419713 | CTLA-4 and PD-1 blockade minimally impacted the cytokine secretion and proliferation of glypican-3-specific T-cells. |
| 575 | 21419713 | These data suggest that CD8(+) T-cell-directed tumor vaccines in HCC may have limited potential for efficacy unless optimal co-stimulation conditions can be identified but CD4(+)-directed vaccines merit consideration. |
| 576 | 21469117 | Here, we show that IL-4 and IL-13 production is NF-κB1-dependent in mouse OVA-specific CD4(+) (OTII) T cells responding to alum-precipitated OVA (alumOVA) immunization. |
| 577 | 21469117 | More surprisingly, we found that NF-κB1 deficiency in OTII cells also selectively impairs their CXCR5 induction by alumOVA without affecting upregulation of BCL6, IL-21, OX40 and CXCR4 mRNA and PD-1 protein. |
| 578 | 21469117 | The selective effects of NF-κB1-deficiency on Th2 and follicular helper T cell induction do not appear to be due to altered expression of the Th2-associated transcription factors - GATA-3, c-Maf and Ikaros. |
| 579 | 21469117 | Altogether, these results suggest that NF-κB1 regulates the expression of CXCR5 on CD4(+) T cells primed in vivo, and thus selectively controls the T-cell-dependent germinal center component of B-cell response to alumOVA. |
| 580 | 21518876 | The IL-6 acted by inducing granzyme B production and reducing expression of inhibitory molecule PD1 on the surface of the primed CD8 T cells. |
| 581 | 21536144 | The 5T33 tumor line, similar to malignant plasma cells from myeloma patients, expresses high levels of programmed death receptor ligand-1 (PD-L1), which binds to the inhibitory receptor, PD-1. |
| 582 | 21536144 | These PD-1(+) T cells were exhausted and produced IL-10. |
| 583 | 21536144 | Inhibition of the PD-1/PD-L1 pathway with HSCT and whole-cell vaccination increased the survival of myeloma-bearing mice from 0% to 40%. |
| 584 | 21536144 | The 5T33 tumor line, similar to malignant plasma cells from myeloma patients, expresses high levels of programmed death receptor ligand-1 (PD-L1), which binds to the inhibitory receptor, PD-1. |
| 585 | 21536144 | These PD-1(+) T cells were exhausted and produced IL-10. |
| 586 | 21536144 | Inhibition of the PD-1/PD-L1 pathway with HSCT and whole-cell vaccination increased the survival of myeloma-bearing mice from 0% to 40%. |
| 587 | 21536144 | The 5T33 tumor line, similar to malignant plasma cells from myeloma patients, expresses high levels of programmed death receptor ligand-1 (PD-L1), which binds to the inhibitory receptor, PD-1. |
| 588 | 21536144 | These PD-1(+) T cells were exhausted and produced IL-10. |
| 589 | 21536144 | Inhibition of the PD-1/PD-L1 pathway with HSCT and whole-cell vaccination increased the survival of myeloma-bearing mice from 0% to 40%. |
| 590 | 21538347 | Combination of lentivector immunization and low-dose chemotherapy or PD-1/PD-L1 blocking primes self-reactive T cells and induces anti-tumor immunity. |
| 591 | 21538347 | We show here that combining rLV vaccination with either cyclophosphamide or PD-1 and PD-L1 blocking antibodies enhances rLV vaccination efficacy and improves anti-tumor immunity. |
| 592 | 21538347 | Combination of lentivector immunization and low-dose chemotherapy or PD-1/PD-L1 blocking primes self-reactive T cells and induces anti-tumor immunity. |
| 593 | 21538347 | We show here that combining rLV vaccination with either cyclophosphamide or PD-1 and PD-L1 blocking antibodies enhances rLV vaccination efficacy and improves anti-tumor immunity. |
| 594 | 21577144 | The PD1/PDL1 pathway is an important element contributing to tumor-mediated immune suppression. |
| 595 | 21700764 | In the context of prostate cancer, the immunotherapy strategies that have garnered the most interest are the therapeutic vaccination strategies, exemplified by sipuleucel-T and PROSTVAC-VF, and immune checkpoint blockade of CTLA-4 and PD-1. |
| 596 | 21717068 | The number of T-bet(+) TILs correlates with better survival of esophageal cancer patients. |
| 597 | 21717068 | Using well-defined mouse models, we have further shown that T-bet and Eomes are both required for the adaptive anti-tumor immunity by regulating T-cell trafficking into the tumor tissue and their effector functions inside the tumor microenvironment. |
| 598 | 21717068 | In order to gain further insight into the tumor immune microenvironment in the upper GI cancer, we have also studied expression levels of co-inhibitory molecules such as B7-H1/PD-L1 and B7-H4 in tissue specimens of esophageal and gastric cancers. |
| 599 | 21717068 | The number of CD3(+) and CD8(+) TILs correlates inversely with expression levels of B7-H4 in samples from esophageal cancer, supporting a role of active immune suppression by inhibitory B7 molecules in the tumor microenvironment. |
| 600 | 21717068 | In addition, TILs show functional exhaustion and express high levels of PD-1 and Tim-3. |
| 601 | 21717068 | Future tumor vaccine design should combine blockade of B7 inhibitory molecules and enhancement of T-bet and Eomes levels within the tumor microenvironment. |
| 602 | 21925469 | We have created a mouse model that reproduces these effects, based on the response of CD8(+) T cells to hepatocellular antigen delivered by an adeno-associated virus (AAV) vector. |
| 603 | 21925469 | Over time, antigen-specific CD8(+) T cells show signs of exhaustion, including high expression of PD-1, and eventually both inflammation and fibrosis resolve. |
| 604 | 22160724 | Antigen-specific CD4 T-cell help rescues exhausted CD8 T cells during chronic viral infection. |
| 605 | 22160724 | CD4 T cells play a critical role in regulating CD8 T-cell responses during chronic viral infection. |
| 606 | 22160724 | Several studies in animal models and humans have shown that the absence of CD4 T-cell help results in severe dysfunction of virus-specific CD8 T cells. |
| 607 | 22160724 | However, whether function can be restored in already exhausted CD8 T cells by providing CD4 T-cell help at a later time remains unexplored. |
| 608 | 22160724 | Adoptive transfer of LCMV-specific CD4 T cells into chronically infected mice restored proliferation and cytokine production by exhausted virus-specific CD8 T cells and reduced viral burden. |
| 609 | 22160724 | Although the transferred CD4 T cells were able to enhance function in exhausted CD8 T cells, these CD4 T cells expressed high levels of the programmed cell death (PD)-1 inhibitory receptor. |
| 610 | 22160724 | Blockade of the PD-1 pathway increased the ability of transferred LCMV-specific CD4 T cells to produce effector cytokines, improved rescue of exhausted CD8 T cells, and resulted in a striking reduction in viral load. |
| 611 | 22160724 | These results suggest that CD4 T-cell immunotherapy alone or in conjunction with blockade of inhibitory receptors may be a promising approach for treating CD8 T-cell dysfunction in chronic infections and cancer. |
| 612 | 22351744 | Novel therapies for metastatic renal cell carcinoma: efforts to expand beyond the VEGF/mTOR signaling paradigm. |
| 613 | 22351744 | However, the goal of cure remains elusive, and the agents nearest approval (i.e., axitinib and tivozanib) abide by the same paradigm as existing drugs (i.e., inhibition of VEGF or mTOR signaling). |
| 614 | 22351744 | Specifically, novel immunotherapeutic strategies will be discussed, including vaccine therapy, cytotoxic T-lymphocyte antigen 4 (CTLA4) blockade, and programmed death-1 (PD-1) inhibition, as well as novel approaches to angiogenesis inhibition, such as abrogation of Ang/Tie-2 signaling. |
| 615 | 22351744 | Pharmacologic strategies to block other potentially relevant signaling pathways, such as fibroblast growth factor receptor or MET inhibition, are also in various stages of development. |
| 616 | 22351744 | Although VEGF and mTOR inhibition have dramatically improved outcomes for patients with mRCCs, a surge above the current plateau with these agents will likely require exploring new avenues. |
| 617 | 22427637 | Bcl6 and Maf cooperate to instruct human follicular helper CD4 T cell differentiation. |
| 618 | 22427637 | The introduction of Bcl6 expression in primary human CD4 T cells resulted in the regulation of a core set of migration genes that enable trafficking to germinal centers: CXCR4, CXCR5, CCR7, and EBI2. |
| 619 | 22427637 | Bcl6 expression also induced a module of protein expression critical for T-B interactions, including SAP, CD40L, PD-1, ICOS, and CXCL13. |
| 620 | 22427637 | This constitutes direct evidence for Bcl6 control of most of these functions and includes three genes known to be loci of severe human genetic immunodeficiencies (CD40L, SH2D1A, and ICOS). |
| 621 | 22427637 | Introduction of Bcl6 did not alter the expression of IL-21 or IL-4, the primary cytokines of human Tfh cells. |
| 622 | 22427637 | Coexpression of Bcl6 and Maf revealed that Bcl6 and Maf cooperate in the induction of CXCR4, PD-1, and ICOS. |
| 623 | 22427637 | Altogether, these findings reveal that Bcl6 and Maf collaborate to orchestrate a suite of genes that define core characteristics of human Tfh cell biology. |
| 624 | 22427637 | Bcl6 and Maf cooperate to instruct human follicular helper CD4 T cell differentiation. |
| 625 | 22427637 | The introduction of Bcl6 expression in primary human CD4 T cells resulted in the regulation of a core set of migration genes that enable trafficking to germinal centers: CXCR4, CXCR5, CCR7, and EBI2. |
| 626 | 22427637 | Bcl6 expression also induced a module of protein expression critical for T-B interactions, including SAP, CD40L, PD-1, ICOS, and CXCL13. |
| 627 | 22427637 | This constitutes direct evidence for Bcl6 control of most of these functions and includes three genes known to be loci of severe human genetic immunodeficiencies (CD40L, SH2D1A, and ICOS). |
| 628 | 22427637 | Introduction of Bcl6 did not alter the expression of IL-21 or IL-4, the primary cytokines of human Tfh cells. |
| 629 | 22427637 | Coexpression of Bcl6 and Maf revealed that Bcl6 and Maf cooperate in the induction of CXCR4, PD-1, and ICOS. |
| 630 | 22427637 | Altogether, these findings reveal that Bcl6 and Maf collaborate to orchestrate a suite of genes that define core characteristics of human Tfh cell biology. |
| 631 | 22441393 | Short-term HAART resulted in a moderate increase in the expression of PD-1 on both CD4(+) and CD8(+) T cells; yet, there was still a significant reduction in viral load and recovery of CD4(+) T cells. |
| 632 | 22441393 | There were no significant changes in the proinflammatory cytokine interleukin-2 (IL-2) or Th-2 cytokines (IL-4, IL-5, and IL-10) in the corresponding samples. |
| 633 | 22570714 | Ova-specific CD8(+) T cells from OT-I mice adoptively transferred to SM-Ova mice started to proliferate in vivo, acquired CD69 and PD-1 but subsequently down-regulated Bcl-2 and disappeared from the periphery, suggesting a mechanism of peripheral deletion. |
| 634 | 22623771 | Aberrant expression of regulatory receptors programmed death-1 (PD-1) and B- and T-lymphocyte attenuator (BTLA) is linked with dysregulation and exhaustion of T lymphocytes during chronic human immunodeficiency virus type 1 (HIV-1) infection; however, less is known about whether a similar process impacts B-lymphocyte function during HIV-1 infection. |
| 635 | 22623771 | Expression of markers that indicate dysregulation (BTLA and PD-1), immune activation (CD95), and proliferation (Ki-67) was evaluated in B cells from HIV-1-infected viremic and aviremic subjects and healthy subjects, in conjunction with immunoglobulin production and CD4 T cell count. |
| 636 | 22623771 | Dysregulation of B lymphocytes was indicated by a marked disruption of peripheral B cell subsets, increased levels of PD-1 expression, and decreased levels of BTLA expression in viremic subjects compared to aviremic subjects and healthy controls. |
| 637 | 22623771 | PD-1 and BTLA were correlated in a divergent fashion with immune activation, CD4 T cell count, and the total plasma IgG level, a functional correlate of B cell dysfunction. |
| 638 | 22623771 | Aberrant expression of regulatory receptors programmed death-1 (PD-1) and B- and T-lymphocyte attenuator (BTLA) is linked with dysregulation and exhaustion of T lymphocytes during chronic human immunodeficiency virus type 1 (HIV-1) infection; however, less is known about whether a similar process impacts B-lymphocyte function during HIV-1 infection. |
| 639 | 22623771 | Expression of markers that indicate dysregulation (BTLA and PD-1), immune activation (CD95), and proliferation (Ki-67) was evaluated in B cells from HIV-1-infected viremic and aviremic subjects and healthy subjects, in conjunction with immunoglobulin production and CD4 T cell count. |
| 640 | 22623771 | Dysregulation of B lymphocytes was indicated by a marked disruption of peripheral B cell subsets, increased levels of PD-1 expression, and decreased levels of BTLA expression in viremic subjects compared to aviremic subjects and healthy controls. |
| 641 | 22623771 | PD-1 and BTLA were correlated in a divergent fashion with immune activation, CD4 T cell count, and the total plasma IgG level, a functional correlate of B cell dysfunction. |
| 642 | 22623771 | Aberrant expression of regulatory receptors programmed death-1 (PD-1) and B- and T-lymphocyte attenuator (BTLA) is linked with dysregulation and exhaustion of T lymphocytes during chronic human immunodeficiency virus type 1 (HIV-1) infection; however, less is known about whether a similar process impacts B-lymphocyte function during HIV-1 infection. |
| 643 | 22623771 | Expression of markers that indicate dysregulation (BTLA and PD-1), immune activation (CD95), and proliferation (Ki-67) was evaluated in B cells from HIV-1-infected viremic and aviremic subjects and healthy subjects, in conjunction with immunoglobulin production and CD4 T cell count. |
| 644 | 22623771 | Dysregulation of B lymphocytes was indicated by a marked disruption of peripheral B cell subsets, increased levels of PD-1 expression, and decreased levels of BTLA expression in viremic subjects compared to aviremic subjects and healthy controls. |
| 645 | 22623771 | PD-1 and BTLA were correlated in a divergent fashion with immune activation, CD4 T cell count, and the total plasma IgG level, a functional correlate of B cell dysfunction. |
| 646 | 22623771 | Aberrant expression of regulatory receptors programmed death-1 (PD-1) and B- and T-lymphocyte attenuator (BTLA) is linked with dysregulation and exhaustion of T lymphocytes during chronic human immunodeficiency virus type 1 (HIV-1) infection; however, less is known about whether a similar process impacts B-lymphocyte function during HIV-1 infection. |
| 647 | 22623771 | Expression of markers that indicate dysregulation (BTLA and PD-1), immune activation (CD95), and proliferation (Ki-67) was evaluated in B cells from HIV-1-infected viremic and aviremic subjects and healthy subjects, in conjunction with immunoglobulin production and CD4 T cell count. |
| 648 | 22623771 | Dysregulation of B lymphocytes was indicated by a marked disruption of peripheral B cell subsets, increased levels of PD-1 expression, and decreased levels of BTLA expression in viremic subjects compared to aviremic subjects and healthy controls. |
| 649 | 22623771 | PD-1 and BTLA were correlated in a divergent fashion with immune activation, CD4 T cell count, and the total plasma IgG level, a functional correlate of B cell dysfunction. |
| 650 | 22754760 | The vaccine triggered upregulation of the immune inhibitory PD-1 signaling pathway and PD-1 blockade dramatically enhanced the rHuAd5-hDCT + anti-4-1BB strategy, resulting in complete regression of growing tumors in > 70% of recipients. |
| 651 | 22754760 | The impact of the combined anti-4-1BB/anti-PD-1 treatment did not manifest as a dramatic enhancement in either the magnitude or functionality of DCT-specific tumor infiltrating lymphocytes relative to either treatment alone. |
| 652 | 22790963 | In this study, we evaluated the efficacy of the combination of IFN-α-transduced tumor cell vaccines and programmed cell death 1 (PD-1) blockade, and investigated the mechanisms of the antitumor effects of the combined therapy. |
| 653 | 22790963 | Immunohistochemical analyses of the therapeutic model showed marked infiltration of CD4(+) cells and CD8(+) cells in the established MC38 tumors of mice treated with both IFN-α and anti-PD-1. |
| 654 | 22808056 | Our results showed that after footpad HSV-1 infection, PD-1 expression increases on immunodominant SSIEFARL peptide specific CD8 T cells. |
| 655 | 22829916 | They also failed to proliferate, showed a significant increase in apoptosis and expressed high levels of the exhaustion marker programmed death-1 (PD-1) and low levels of the lymphocyte-activation gene 3 (LAG-3). |
| 656 | 22837483 | Binding of this receptor to its ligands, B7-H1 (PD-L1) and B7-DC (PD-L2), attenuates T cell activation, reduces IL-2 and IFN-γ secretion, decreases proliferation and cytotoxicity, and induces apoptosis. |
| 657 | 22837483 | We found that these differences play critical roles in anti-tumor immune effect exhibited by B7-DC-Ig through inhibiting proliferation of PD-1(high) CD4 T cells, leading to a significant decrease in the level of these cells, which are enriched for regulatory T cells, within the tumor. |
| 658 | 22837483 | In addition, it also leads to a decrease in PD-1(high) CD8 T cells, tipping the balance toward nonexhausted functional PD-1(low) CD8 T cells. |
| 659 | 22837483 | Binding of this receptor to its ligands, B7-H1 (PD-L1) and B7-DC (PD-L2), attenuates T cell activation, reduces IL-2 and IFN-γ secretion, decreases proliferation and cytotoxicity, and induces apoptosis. |
| 660 | 22837483 | We found that these differences play critical roles in anti-tumor immune effect exhibited by B7-DC-Ig through inhibiting proliferation of PD-1(high) CD4 T cells, leading to a significant decrease in the level of these cells, which are enriched for regulatory T cells, within the tumor. |
| 661 | 22837483 | In addition, it also leads to a decrease in PD-1(high) CD8 T cells, tipping the balance toward nonexhausted functional PD-1(low) CD8 T cells. |
| 662 | 22878899 | T cell profiling reveals high CD4+CTLA-4 + T cell frequency as dominant predictor for survival after prostate GVAX/ipilimumab treatment. |
| 663 | 22878899 | Treatment-induced rises in absolute lymphocyte counts, CD4(+) T cell differentiation, and CD4(+) and CD8(+) T cell activation were all associated with clinical benefit. |
| 664 | 22878899 | Moreover, significantly prolonged overall survival (OS) was observed for patients with high pre-treatment frequencies of CD4(+)CTLA-4(+), CD4(+)PD-1(+), or differentiated (i.e., non-naive) CD8(+) T cells or low pre-treatment frequencies of differentiated CD4(+) or regulatory T cells. |
| 665 | 22878899 | Unsupervised clustering of these immune biomarkers revealed cancer-related expression of CTLA-4(+) in CD4(+) T cells to be a dominant predictor for survival after Prostate GVAX/ipilimumab therapy and to thus provide a putative and much-needed biomarker for patient selection prior to therapeutic CTLA4 blockade. |
| 666 | 22903545 | BTLA (B- and T-lymphocyte attenuator) is a prominent co-receptor that is structurally and functionally related to CTLA-4 and PD-1. |
| 667 | 22903545 | Upon ligation with HVEM, BTLA inhibited CpG-mediated B cell functions (proliferation, cytokine production, and upregulation of co-stimulatory molecules), which was reversed by blocking BTLA/HVEM interactions. |
| 668 | 22903545 | Interestingly, chemokine secretion (IL-8 and MIP1β) was not affected by BTLA/HVEM ligation, suggesting that BTLA-mediated inhibition is selective for some but not all B cell functions. |
| 669 | 22918927 | For example, in preclinical investigations, combined blockade of programmed death-1 (PD1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), which have key roles in the negative regulation of T-cell activation, has been shown to enhance antitumour immune responses compared with either agent alone. |
| 670 | 23071696 | CD154 and IL-2 signaling of CD4+ T cells play a critical role in multiple phases of CD8+ CTL responses following adenovirus vaccination. |
| 671 | 23071696 | While the role of CD8(+) cytotoxic T lymphocyte (CTL) responses in mediating AdV-induced protection is well understood, the involvement of CD4(+) T cell-provided signals in the development of functional CD8(+) CTL responses remain unclear. |
| 672 | 23071696 | Without CD4(+) T help, both primary and memory CTL responses were greatly reduced in this model, and were associated with increased PD-1 expression. |
| 673 | 23071696 | These effects were specifically mediated by CD4(+) T cell-produced IL-2 and CD154 signals. |
| 674 | 23135914 | In explaining this paradoxical result, we showed that these PD-1(+) T cells expressed activation markers and were functional after blockade of the PD-1-PD-L1 axis in vitro. |
| 675 | 23135914 | Approximately 50% of PD-1(+) tumor-infiltrating T cells lacked Tim-3 expression and may indeed represent activated T cells. |
| 676 | 23135914 | Our findings prompt a need to revisit the significance of PD-1-infiltrating T cells in cancer, where we suggest that PD-1 detection may reflect a previous immune response against tumors that might be reactivated by PD-1/PD-L1 blockade. |
| 677 | 23135914 | In explaining this paradoxical result, we showed that these PD-1(+) T cells expressed activation markers and were functional after blockade of the PD-1-PD-L1 axis in vitro. |
| 678 | 23135914 | Approximately 50% of PD-1(+) tumor-infiltrating T cells lacked Tim-3 expression and may indeed represent activated T cells. |
| 679 | 23135914 | Our findings prompt a need to revisit the significance of PD-1-infiltrating T cells in cancer, where we suggest that PD-1 detection may reflect a previous immune response against tumors that might be reactivated by PD-1/PD-L1 blockade. |
| 680 | 23135914 | In explaining this paradoxical result, we showed that these PD-1(+) T cells expressed activation markers and were functional after blockade of the PD-1-PD-L1 axis in vitro. |
| 681 | 23135914 | Approximately 50% of PD-1(+) tumor-infiltrating T cells lacked Tim-3 expression and may indeed represent activated T cells. |
| 682 | 23135914 | Our findings prompt a need to revisit the significance of PD-1-infiltrating T cells in cancer, where we suggest that PD-1 detection may reflect a previous immune response against tumors that might be reactivated by PD-1/PD-L1 blockade. |
| 683 | 23162125 | We demonstrate that neonatal immunization induces CXCR5(high)PD-1(high) CD4(+) T(FH) cells that exhibit T(FH) features (including Batf, Bcl6, c-Maf, ICOS, and IL-21 expression) and are able to migrate into the GCs. |
| 684 | 23175378 | However, based on a multidimensional analysis of CD45RO, CD27, CCR7, CD127, CD57, and PD-1 expression, we found that individuals living in regions with intense and perennial (holoendemic) malaria transmission harbored more differentiated EBV-specific CD8(+) T-cell populations that contained fewer central memory cells than individuals living in regions with little or no (hypoendemic) malaria. |
| 685 | 23267892 | [Prediction of WT1/MUC1 peptide dendritic cell therapy responders by quantification of ex vivo induced mRNA in whole blood]. |
| 686 | 23267892 | To challenge this classic problem, we quantified 17 different leukocyte function-associated mRNAs( IFN-γ,TNFSF1, TNFSF2, TNFSF5, IL-10, TGF β,CTLA4, PD1, FOXP3, GMCSF, VEGF, IL-8, CCL8, CXCL3, and IL-2) in whole blood after ex vivo stimulation with 7 different agents(PHA, HAG, zymosan, IFN-γ,rIL-2, aTCR, and picibanil) to activate various subsets of leukocytes. |
| 687 | 23267892 | The clinical outcomes for WT1 peptide-and/or MUC1 peptide-pulsed dendritic cell therapy for advanced cancer (n=26) were CR+PR, 4 cases; SD, 9 cases; and PD, 13 cases. |
| 688 | 23325679 | Antibodies to gp120 and PD-1 expression on virus-specific CD8+ T cells in protection from simian AIDS. |
| 689 | 23325679 | We compared the relative efficacies against simian immunodeficiency virus (SIV) challenge of three vaccine regimens that elicited similar frequencies of SIV-specific CD4(+) and CD8(+) T-cell responses but differed in the level of antibody responses to the gp120 envelope protein. |
| 690 | 23325679 | Mamu-A*01 macaques of this third group exhibited persistent Gag CD8(+)CM9(+) effector memory T cells with low expression of surface Programmed death-1 (PD-1) receptor and high levels of expression of genes associated with major histocompatibility complex class I (MHC-I) and MHC-II antigen. |
| 691 | 23325679 | The fact that control of SIV replication was associated with both high titers of antibodies to the SIV envelope protein and durable effector SIV-specific CD8(+) T cells suggests the hypothesis that the presence of antibodies at the time of challenge may increase innate immune recruiting activity by enhancing antigen uptake and may result in improvement of the quality and potency of secondary SIV-specific CD8(+) T-cell responses. |
| 692 | 23325679 | Antibodies to gp120 and PD-1 expression on virus-specific CD8+ T cells in protection from simian AIDS. |
| 693 | 23325679 | We compared the relative efficacies against simian immunodeficiency virus (SIV) challenge of three vaccine regimens that elicited similar frequencies of SIV-specific CD4(+) and CD8(+) T-cell responses but differed in the level of antibody responses to the gp120 envelope protein. |
| 694 | 23325679 | Mamu-A*01 macaques of this third group exhibited persistent Gag CD8(+)CM9(+) effector memory T cells with low expression of surface Programmed death-1 (PD-1) receptor and high levels of expression of genes associated with major histocompatibility complex class I (MHC-I) and MHC-II antigen. |
| 695 | 23325679 | The fact that control of SIV replication was associated with both high titers of antibodies to the SIV envelope protein and durable effector SIV-specific CD8(+) T cells suggests the hypothesis that the presence of antibodies at the time of challenge may increase innate immune recruiting activity by enhancing antigen uptake and may result in improvement of the quality and potency of secondary SIV-specific CD8(+) T-cell responses. |
| 696 | 23337984 | Adenovirus expressing both thymidine kinase and soluble PD1 enhances antitumor immunity by strengthening CD8 T-cell response. |
| 697 | 23337984 | Programmed death ligand 1 (PD-L1) expressed on tumor cell surfaces mediates tumor-induced immunoresistance by inhibiting PD1-expressing tumor-infiltrating T cells. |
| 698 | 23337984 | Here, we explored whether a soluble form of PD1 (sPD1-Ig), which blocks PD-L1, could synergize with TERT-TR-regulated HSVtk to enhance the adenoviral therapeutic efficacy by boosting antitumor immunity. |
| 699 | 23337984 | Consistent with this, following adoptive transfer of tumor antigen-specific CD8 T cells into tumor-bearing Rag1(-/-) mice, dual-module adenovirus significantly enhanced CD8 T cell-mediated tumor rejection. |
| 700 | 23337984 | Adenovirus expressing both thymidine kinase and soluble PD1 enhances antitumor immunity by strengthening CD8 T-cell response. |
| 701 | 23337984 | Programmed death ligand 1 (PD-L1) expressed on tumor cell surfaces mediates tumor-induced immunoresistance by inhibiting PD1-expressing tumor-infiltrating T cells. |
| 702 | 23337984 | Here, we explored whether a soluble form of PD1 (sPD1-Ig), which blocks PD-L1, could synergize with TERT-TR-regulated HSVtk to enhance the adenoviral therapeutic efficacy by boosting antitumor immunity. |
| 703 | 23337984 | Consistent with this, following adoptive transfer of tumor antigen-specific CD8 T cells into tumor-bearing Rag1(-/-) mice, dual-module adenovirus significantly enhanced CD8 T cell-mediated tumor rejection. |
| 704 | 23337984 | Adenovirus expressing both thymidine kinase and soluble PD1 enhances antitumor immunity by strengthening CD8 T-cell response. |
| 705 | 23337984 | Programmed death ligand 1 (PD-L1) expressed on tumor cell surfaces mediates tumor-induced immunoresistance by inhibiting PD1-expressing tumor-infiltrating T cells. |
| 706 | 23337984 | Here, we explored whether a soluble form of PD1 (sPD1-Ig), which blocks PD-L1, could synergize with TERT-TR-regulated HSVtk to enhance the adenoviral therapeutic efficacy by boosting antitumor immunity. |
| 707 | 23337984 | Consistent with this, following adoptive transfer of tumor antigen-specific CD8 T cells into tumor-bearing Rag1(-/-) mice, dual-module adenovirus significantly enhanced CD8 T cell-mediated tumor rejection. |
| 708 | 23338234 | Furthermore, HLA-A2- and HLA-B7-restricted YFV epitope-specific effector cells predominantly displayed a CD45RA(-)CCR7(-)PD-1(+)CD27(high) phenotype, which transitioned into a CD45RA(+)CCR7(-)PD-1(-)CD27(low) memory population phenotype. |
| 709 | 23338234 | Interestingly, activation of CD4 T cells, as well as FOXP3(+) T regulatory cells, in response to YFV vaccination preceded the kinetics of the CD8 T cell response. |
| 710 | 23401435 | Blocking inhibitory pathways via monoclonal antibodies, such as the anti-cytotoxic T-lymphocyte antigen-4 antibody (ipilimumab), anti-programmed cell death-1 antibody (BMS-936558), and anti-programmed cell death-1 ligand antibody (BMS-936559), has the ability to break down the shield that tumors co-opt for their defense. |
| 711 | 23401435 | Newer vaccines, particularly the tumor cell vaccine, belagenpumatucel-L, and the antigen-specific vaccines, melanoma-associated antigen-A3, liposomal BLP-25, TG4010, and recombinant human epidermal growth factor, are being evaluated in some of the largest trials ever attempted in lung cancer therapy. |
| 712 | 23404195 | Non-specific immunotherapy has been for a long time a standard treatment option for patients with metastatic renal cell carcinoma but was redeemed by specific targeted molecular therapies, namely the VEGF and mTOR inhibitors. |
| 713 | 23404195 | In addition, different combinatory strategies with immunomodulating agents like cyclophosphamide or sunitinib are outlined, and the effects of immune checkpoint modulators as anti-CTLA-4 or PD-1 antibodies are discussed. |
| 714 | 23475201 | In fact, we show that engagement of PD-1 on TFH cells leads to a reduction in cell proliferation, activation, inducible T-cell co-stimulator (ICOS) expression and interleukin-21 (IL-21) cytokine secretion. |
| 715 | 23475201 | We further show that at least part of this defect involves IL-21, as addition of this cytokine rescues antibody responses and plasma cell generation in vitro. |
| 716 | 23523609 | Blockade of PD-1/PD-L1 immune checkpoint during DC vaccination induces potent protective immunity against breast cancer in hu-SCID mice. |
| 717 | 23523609 | Immune checkpoints, such as the PD-1/PD-L1 pathway, negatively interfere in the efficiency of dendritic cell (DC) vaccination in cancer immunotherapy. |
| 718 | 23523609 | Blockade of PD-1/PD-L1 immune checkpoint during DC vaccination induces potent protective immunity against breast cancer in hu-SCID mice. |
| 719 | 23523609 | Immune checkpoints, such as the PD-1/PD-L1 pathway, negatively interfere in the efficiency of dendritic cell (DC) vaccination in cancer immunotherapy. |
| 720 | 23548749 | In addition, cell-based measurements of virus persistence equate with activation markers and the frequency of CD4 T cells expressing PD-1. |
| 721 | 23548749 | High-level expression of PD-1 and its ligands PD-L1 and PD-L2 are found on hematopoietic and non-hematopoietic cells, and are upregulated by chronic antigen stimulation, Type 1 and Type II interferons (IFNs), and homeostatic cytokines. |
| 722 | 23548749 | In HIV infected subjects, PD-1 levels on CD4 and CD8 T cells continue to remain high following combination anti-retroviral therapy (cART). |
| 723 | 23548749 | System biology approaches have begun to elucidate signal transduction pathways regulated by PD-1 expression in CD4 and CD8 T cell subsets that become dysfunctional through chronic TCR activation and PD-1 signaling. |
| 724 | 23548749 | In addition, cell-based measurements of virus persistence equate with activation markers and the frequency of CD4 T cells expressing PD-1. |
| 725 | 23548749 | High-level expression of PD-1 and its ligands PD-L1 and PD-L2 are found on hematopoietic and non-hematopoietic cells, and are upregulated by chronic antigen stimulation, Type 1 and Type II interferons (IFNs), and homeostatic cytokines. |
| 726 | 23548749 | In HIV infected subjects, PD-1 levels on CD4 and CD8 T cells continue to remain high following combination anti-retroviral therapy (cART). |
| 727 | 23548749 | System biology approaches have begun to elucidate signal transduction pathways regulated by PD-1 expression in CD4 and CD8 T cell subsets that become dysfunctional through chronic TCR activation and PD-1 signaling. |
| 728 | 23548749 | In addition, cell-based measurements of virus persistence equate with activation markers and the frequency of CD4 T cells expressing PD-1. |
| 729 | 23548749 | High-level expression of PD-1 and its ligands PD-L1 and PD-L2 are found on hematopoietic and non-hematopoietic cells, and are upregulated by chronic antigen stimulation, Type 1 and Type II interferons (IFNs), and homeostatic cytokines. |
| 730 | 23548749 | In HIV infected subjects, PD-1 levels on CD4 and CD8 T cells continue to remain high following combination anti-retroviral therapy (cART). |
| 731 | 23548749 | System biology approaches have begun to elucidate signal transduction pathways regulated by PD-1 expression in CD4 and CD8 T cell subsets that become dysfunctional through chronic TCR activation and PD-1 signaling. |
| 732 | 23548749 | In addition, cell-based measurements of virus persistence equate with activation markers and the frequency of CD4 T cells expressing PD-1. |
| 733 | 23548749 | High-level expression of PD-1 and its ligands PD-L1 and PD-L2 are found on hematopoietic and non-hematopoietic cells, and are upregulated by chronic antigen stimulation, Type 1 and Type II interferons (IFNs), and homeostatic cytokines. |
| 734 | 23548749 | In HIV infected subjects, PD-1 levels on CD4 and CD8 T cells continue to remain high following combination anti-retroviral therapy (cART). |
| 735 | 23548749 | System biology approaches have begun to elucidate signal transduction pathways regulated by PD-1 expression in CD4 and CD8 T cell subsets that become dysfunctional through chronic TCR activation and PD-1 signaling. |
| 736 | 23587922 | Δ42PD1 appears to function distinctly from PD1, as it does not engage PD-L1/PD-L2 but its recombinant form could induce proinflammatory cytokines. |
| 737 | 23633484 | Dual blockade of PD-1 and CTLA-4 combined with tumor vaccine effectively restores T-cell rejection function in tumors. |
| 738 | 23633484 | In this study, we document parallel regulation of CD8(+) T cells and Foxp3(+) Tregs by programmed death-1 (PD-1, PDCD1). |
| 739 | 23633484 | In addition, we identify an additional role of CTL antigen-4 (CTLA-4) inhibitory receptor in further promoting dysfunction of CD8(+) T effector cells in tumor models (CT26 colon carcinoma and ID8-VEGF ovarian carcinoma). |
| 740 | 23633484 | Two thirds of CD8(+) tumor-infiltrating lymphocytes (TIL) expressed PD-1, whereas one third to half of CD8(+) TIL coexpressed PD-1 and CTLA-4. |
| 741 | 23633484 | Double-positive (PD-1(+)CTLA-4(+)) CD8(+) TIL had characteristics of more severe dysfunction than single-positive (PD-1(+) or CTLA-4(+)) TIL, including an inability to proliferate and secrete effector cytokines. |
| 742 | 23633484 | Blockade of both PD-1 and CTLA-4 resulted in reversal of CD8(+) TIL dysfunction and led to tumor rejection in two thirds of mice. |
| 743 | 23633484 | Double blockade was associated with increased proliferation of antigen-specific effector CD8(+) and CD4(+) T cells, antigen-specific cytokine release, inhibition of suppressive functions of Tregs, and upregulation of key signaling molecules critical for T-cell function. |
| 744 | 23633484 | When used in combination with GVAX vaccination (consisting of granulocyte macrophage colony-stimulating factor-expressing irradiated tumor cells), inhibitory pathway blockade induced rejection of CT26 tumors in 100% of mice and ID8-VEGF tumors in 75% of mice. |
| 745 | 23633484 | Our study indicates that PD-1 signaling in tumors is required for both suppressing effector T cells and maintaining tumor Tregs, and that PD-1/PD-L1 pathway (CD274) blockade augments tumor inhibition by increasing effector T-cell activity, thereby attenuating Treg suppression. |
| 746 | 23633484 | Dual blockade of PD-1 and CTLA-4 combined with tumor vaccine effectively restores T-cell rejection function in tumors. |
| 747 | 23633484 | In this study, we document parallel regulation of CD8(+) T cells and Foxp3(+) Tregs by programmed death-1 (PD-1, PDCD1). |
| 748 | 23633484 | In addition, we identify an additional role of CTL antigen-4 (CTLA-4) inhibitory receptor in further promoting dysfunction of CD8(+) T effector cells in tumor models (CT26 colon carcinoma and ID8-VEGF ovarian carcinoma). |
| 749 | 23633484 | Two thirds of CD8(+) tumor-infiltrating lymphocytes (TIL) expressed PD-1, whereas one third to half of CD8(+) TIL coexpressed PD-1 and CTLA-4. |
| 750 | 23633484 | Double-positive (PD-1(+)CTLA-4(+)) CD8(+) TIL had characteristics of more severe dysfunction than single-positive (PD-1(+) or CTLA-4(+)) TIL, including an inability to proliferate and secrete effector cytokines. |
| 751 | 23633484 | Blockade of both PD-1 and CTLA-4 resulted in reversal of CD8(+) TIL dysfunction and led to tumor rejection in two thirds of mice. |
| 752 | 23633484 | Double blockade was associated with increased proliferation of antigen-specific effector CD8(+) and CD4(+) T cells, antigen-specific cytokine release, inhibition of suppressive functions of Tregs, and upregulation of key signaling molecules critical for T-cell function. |
| 753 | 23633484 | When used in combination with GVAX vaccination (consisting of granulocyte macrophage colony-stimulating factor-expressing irradiated tumor cells), inhibitory pathway blockade induced rejection of CT26 tumors in 100% of mice and ID8-VEGF tumors in 75% of mice. |
| 754 | 23633484 | Our study indicates that PD-1 signaling in tumors is required for both suppressing effector T cells and maintaining tumor Tregs, and that PD-1/PD-L1 pathway (CD274) blockade augments tumor inhibition by increasing effector T-cell activity, thereby attenuating Treg suppression. |
| 755 | 23633484 | Dual blockade of PD-1 and CTLA-4 combined with tumor vaccine effectively restores T-cell rejection function in tumors. |
| 756 | 23633484 | In this study, we document parallel regulation of CD8(+) T cells and Foxp3(+) Tregs by programmed death-1 (PD-1, PDCD1). |
| 757 | 23633484 | In addition, we identify an additional role of CTL antigen-4 (CTLA-4) inhibitory receptor in further promoting dysfunction of CD8(+) T effector cells in tumor models (CT26 colon carcinoma and ID8-VEGF ovarian carcinoma). |
| 758 | 23633484 | Two thirds of CD8(+) tumor-infiltrating lymphocytes (TIL) expressed PD-1, whereas one third to half of CD8(+) TIL coexpressed PD-1 and CTLA-4. |
| 759 | 23633484 | Double-positive (PD-1(+)CTLA-4(+)) CD8(+) TIL had characteristics of more severe dysfunction than single-positive (PD-1(+) or CTLA-4(+)) TIL, including an inability to proliferate and secrete effector cytokines. |
| 760 | 23633484 | Blockade of both PD-1 and CTLA-4 resulted in reversal of CD8(+) TIL dysfunction and led to tumor rejection in two thirds of mice. |
| 761 | 23633484 | Double blockade was associated with increased proliferation of antigen-specific effector CD8(+) and CD4(+) T cells, antigen-specific cytokine release, inhibition of suppressive functions of Tregs, and upregulation of key signaling molecules critical for T-cell function. |
| 762 | 23633484 | When used in combination with GVAX vaccination (consisting of granulocyte macrophage colony-stimulating factor-expressing irradiated tumor cells), inhibitory pathway blockade induced rejection of CT26 tumors in 100% of mice and ID8-VEGF tumors in 75% of mice. |
| 763 | 23633484 | Our study indicates that PD-1 signaling in tumors is required for both suppressing effector T cells and maintaining tumor Tregs, and that PD-1/PD-L1 pathway (CD274) blockade augments tumor inhibition by increasing effector T-cell activity, thereby attenuating Treg suppression. |
| 764 | 23633484 | Dual blockade of PD-1 and CTLA-4 combined with tumor vaccine effectively restores T-cell rejection function in tumors. |
| 765 | 23633484 | In this study, we document parallel regulation of CD8(+) T cells and Foxp3(+) Tregs by programmed death-1 (PD-1, PDCD1). |
| 766 | 23633484 | In addition, we identify an additional role of CTL antigen-4 (CTLA-4) inhibitory receptor in further promoting dysfunction of CD8(+) T effector cells in tumor models (CT26 colon carcinoma and ID8-VEGF ovarian carcinoma). |
| 767 | 23633484 | Two thirds of CD8(+) tumor-infiltrating lymphocytes (TIL) expressed PD-1, whereas one third to half of CD8(+) TIL coexpressed PD-1 and CTLA-4. |
| 768 | 23633484 | Double-positive (PD-1(+)CTLA-4(+)) CD8(+) TIL had characteristics of more severe dysfunction than single-positive (PD-1(+) or CTLA-4(+)) TIL, including an inability to proliferate and secrete effector cytokines. |
| 769 | 23633484 | Blockade of both PD-1 and CTLA-4 resulted in reversal of CD8(+) TIL dysfunction and led to tumor rejection in two thirds of mice. |
| 770 | 23633484 | Double blockade was associated with increased proliferation of antigen-specific effector CD8(+) and CD4(+) T cells, antigen-specific cytokine release, inhibition of suppressive functions of Tregs, and upregulation of key signaling molecules critical for T-cell function. |
| 771 | 23633484 | When used in combination with GVAX vaccination (consisting of granulocyte macrophage colony-stimulating factor-expressing irradiated tumor cells), inhibitory pathway blockade induced rejection of CT26 tumors in 100% of mice and ID8-VEGF tumors in 75% of mice. |
| 772 | 23633484 | Our study indicates that PD-1 signaling in tumors is required for both suppressing effector T cells and maintaining tumor Tregs, and that PD-1/PD-L1 pathway (CD274) blockade augments tumor inhibition by increasing effector T-cell activity, thereby attenuating Treg suppression. |
| 773 | 23633484 | Dual blockade of PD-1 and CTLA-4 combined with tumor vaccine effectively restores T-cell rejection function in tumors. |
| 774 | 23633484 | In this study, we document parallel regulation of CD8(+) T cells and Foxp3(+) Tregs by programmed death-1 (PD-1, PDCD1). |
| 775 | 23633484 | In addition, we identify an additional role of CTL antigen-4 (CTLA-4) inhibitory receptor in further promoting dysfunction of CD8(+) T effector cells in tumor models (CT26 colon carcinoma and ID8-VEGF ovarian carcinoma). |
| 776 | 23633484 | Two thirds of CD8(+) tumor-infiltrating lymphocytes (TIL) expressed PD-1, whereas one third to half of CD8(+) TIL coexpressed PD-1 and CTLA-4. |
| 777 | 23633484 | Double-positive (PD-1(+)CTLA-4(+)) CD8(+) TIL had characteristics of more severe dysfunction than single-positive (PD-1(+) or CTLA-4(+)) TIL, including an inability to proliferate and secrete effector cytokines. |
| 778 | 23633484 | Blockade of both PD-1 and CTLA-4 resulted in reversal of CD8(+) TIL dysfunction and led to tumor rejection in two thirds of mice. |
| 779 | 23633484 | Double blockade was associated with increased proliferation of antigen-specific effector CD8(+) and CD4(+) T cells, antigen-specific cytokine release, inhibition of suppressive functions of Tregs, and upregulation of key signaling molecules critical for T-cell function. |
| 780 | 23633484 | When used in combination with GVAX vaccination (consisting of granulocyte macrophage colony-stimulating factor-expressing irradiated tumor cells), inhibitory pathway blockade induced rejection of CT26 tumors in 100% of mice and ID8-VEGF tumors in 75% of mice. |
| 781 | 23633484 | Our study indicates that PD-1 signaling in tumors is required for both suppressing effector T cells and maintaining tumor Tregs, and that PD-1/PD-L1 pathway (CD274) blockade augments tumor inhibition by increasing effector T-cell activity, thereby attenuating Treg suppression. |
| 782 | 23633484 | Dual blockade of PD-1 and CTLA-4 combined with tumor vaccine effectively restores T-cell rejection function in tumors. |
| 783 | 23633484 | In this study, we document parallel regulation of CD8(+) T cells and Foxp3(+) Tregs by programmed death-1 (PD-1, PDCD1). |
| 784 | 23633484 | In addition, we identify an additional role of CTL antigen-4 (CTLA-4) inhibitory receptor in further promoting dysfunction of CD8(+) T effector cells in tumor models (CT26 colon carcinoma and ID8-VEGF ovarian carcinoma). |
| 785 | 23633484 | Two thirds of CD8(+) tumor-infiltrating lymphocytes (TIL) expressed PD-1, whereas one third to half of CD8(+) TIL coexpressed PD-1 and CTLA-4. |
| 786 | 23633484 | Double-positive (PD-1(+)CTLA-4(+)) CD8(+) TIL had characteristics of more severe dysfunction than single-positive (PD-1(+) or CTLA-4(+)) TIL, including an inability to proliferate and secrete effector cytokines. |
| 787 | 23633484 | Blockade of both PD-1 and CTLA-4 resulted in reversal of CD8(+) TIL dysfunction and led to tumor rejection in two thirds of mice. |
| 788 | 23633484 | Double blockade was associated with increased proliferation of antigen-specific effector CD8(+) and CD4(+) T cells, antigen-specific cytokine release, inhibition of suppressive functions of Tregs, and upregulation of key signaling molecules critical for T-cell function. |
| 789 | 23633484 | When used in combination with GVAX vaccination (consisting of granulocyte macrophage colony-stimulating factor-expressing irradiated tumor cells), inhibitory pathway blockade induced rejection of CT26 tumors in 100% of mice and ID8-VEGF tumors in 75% of mice. |
| 790 | 23633484 | Our study indicates that PD-1 signaling in tumors is required for both suppressing effector T cells and maintaining tumor Tregs, and that PD-1/PD-L1 pathway (CD274) blockade augments tumor inhibition by increasing effector T-cell activity, thereby attenuating Treg suppression. |
| 791 | 23635778 | Here, we report the development of what we believe to be a novel antigen-targeting DNA vaccine strategy that exploits the binding of programmed death-1 (PD1) to its ligands expressed on dendritic cells (DCs) by fusing soluble PD1 with HIV-1 GAG p24 antigen. |
| 792 | 23644506 | During chronic infection, pathogen-specific CD8(+) T cells upregulate expression of molecules such as the inhibitory surface receptor PD-1, have diminished cytokine production and are thought to undergo terminal differentiation into exhausted cells. |
| 793 | 23676462 | PD-L1 blockade synergizes with IL-2 therapy in reinvigorating exhausted T cells. |
| 794 | 23676462 | To address this issue, we examined the effect of IL-2 and PD-1 ligand 1 (PD-L1) blockade in the mouse model of chronic lymphocytic choriomeningitis virus (LCMV) infection. |
| 795 | 23676462 | We found that low-dose IL-2 administration alone enhanced CD8+ T cell responses in chronically infected mice. |
| 796 | 23676462 | IL-2 treatment also decreased inhibitory receptor levels on virus-specific CD8+ T cells and increased expression of CD127 and CD44, resulting in a phenotype resembling that of memory T cells. |
| 797 | 23676462 | However, combining IL-2 treatment with blockade of the PD-1 inhibitory pathway had striking synergistic effects in enhancing virus-specific CD8+ T cell responses and decreasing viral load. |
| 798 | 23676462 | These results suggest that combined IL-2 therapy and PD-L1 blockade merits consideration as a regimen for treating human chronic infections and cancer. |
| 799 | 23676462 | PD-L1 blockade synergizes with IL-2 therapy in reinvigorating exhausted T cells. |
| 800 | 23676462 | To address this issue, we examined the effect of IL-2 and PD-1 ligand 1 (PD-L1) blockade in the mouse model of chronic lymphocytic choriomeningitis virus (LCMV) infection. |
| 801 | 23676462 | We found that low-dose IL-2 administration alone enhanced CD8+ T cell responses in chronically infected mice. |
| 802 | 23676462 | IL-2 treatment also decreased inhibitory receptor levels on virus-specific CD8+ T cells and increased expression of CD127 and CD44, resulting in a phenotype resembling that of memory T cells. |
| 803 | 23676462 | However, combining IL-2 treatment with blockade of the PD-1 inhibitory pathway had striking synergistic effects in enhancing virus-specific CD8+ T cell responses and decreasing viral load. |
| 804 | 23676462 | These results suggest that combined IL-2 therapy and PD-L1 blockade merits consideration as a regimen for treating human chronic infections and cancer. |
| 805 | 23759470 | In our current study, we found that LBP were able to activate CXCR5+PD-1+ Tfh cells and induce IL-21 secretion. |
| 806 | 23772031 | Cutting edge: Prolonged exposure to HIV reinforces a poised epigenetic program for PD-1 expression in virus-specific CD8 T cells. |
| 807 | 23772031 | Ag-specific CD8 T cells play a critical role in controlling HIV infection but eventually lose antiviral functions in part because of expression and signaling through the inhibitory programmed death-1 (PD-1) receptor. |
| 808 | 23772031 | To better understand the impact of prolonged TCR ligation on regulation of PD-1 expression in HIV-specific CD8 T cells, we investigated the capacity of virus-specific CD8 T cells to modify the PD-1 epigenetic program after reduction in viral load. |
| 809 | 23772031 | We observed that the transcriptional regulatory region was unmethylated in the PD-1(hi) HIV-specific CD8 T cells, whereas it remained methylated in donor-matched naive cells at acute and chronic stages of infection. |
| 810 | 23772031 | Surprisingly, the PD-1 promoter remained unmethylated in HIV-specific CD8 T cells from subjects with a viral load controlled by antiviral therapy for >2 y or from elite controllers. |
| 811 | 23772031 | Cutting edge: Prolonged exposure to HIV reinforces a poised epigenetic program for PD-1 expression in virus-specific CD8 T cells. |
| 812 | 23772031 | Ag-specific CD8 T cells play a critical role in controlling HIV infection but eventually lose antiviral functions in part because of expression and signaling through the inhibitory programmed death-1 (PD-1) receptor. |
| 813 | 23772031 | To better understand the impact of prolonged TCR ligation on regulation of PD-1 expression in HIV-specific CD8 T cells, we investigated the capacity of virus-specific CD8 T cells to modify the PD-1 epigenetic program after reduction in viral load. |
| 814 | 23772031 | We observed that the transcriptional regulatory region was unmethylated in the PD-1(hi) HIV-specific CD8 T cells, whereas it remained methylated in donor-matched naive cells at acute and chronic stages of infection. |
| 815 | 23772031 | Surprisingly, the PD-1 promoter remained unmethylated in HIV-specific CD8 T cells from subjects with a viral load controlled by antiviral therapy for >2 y or from elite controllers. |
| 816 | 23772031 | Cutting edge: Prolonged exposure to HIV reinforces a poised epigenetic program for PD-1 expression in virus-specific CD8 T cells. |
| 817 | 23772031 | Ag-specific CD8 T cells play a critical role in controlling HIV infection but eventually lose antiviral functions in part because of expression and signaling through the inhibitory programmed death-1 (PD-1) receptor. |
| 818 | 23772031 | To better understand the impact of prolonged TCR ligation on regulation of PD-1 expression in HIV-specific CD8 T cells, we investigated the capacity of virus-specific CD8 T cells to modify the PD-1 epigenetic program after reduction in viral load. |
| 819 | 23772031 | We observed that the transcriptional regulatory region was unmethylated in the PD-1(hi) HIV-specific CD8 T cells, whereas it remained methylated in donor-matched naive cells at acute and chronic stages of infection. |
| 820 | 23772031 | Surprisingly, the PD-1 promoter remained unmethylated in HIV-specific CD8 T cells from subjects with a viral load controlled by antiviral therapy for >2 y or from elite controllers. |
| 821 | 23772031 | Cutting edge: Prolonged exposure to HIV reinforces a poised epigenetic program for PD-1 expression in virus-specific CD8 T cells. |
| 822 | 23772031 | Ag-specific CD8 T cells play a critical role in controlling HIV infection but eventually lose antiviral functions in part because of expression and signaling through the inhibitory programmed death-1 (PD-1) receptor. |
| 823 | 23772031 | To better understand the impact of prolonged TCR ligation on regulation of PD-1 expression in HIV-specific CD8 T cells, we investigated the capacity of virus-specific CD8 T cells to modify the PD-1 epigenetic program after reduction in viral load. |
| 824 | 23772031 | We observed that the transcriptional regulatory region was unmethylated in the PD-1(hi) HIV-specific CD8 T cells, whereas it remained methylated in donor-matched naive cells at acute and chronic stages of infection. |
| 825 | 23772031 | Surprisingly, the PD-1 promoter remained unmethylated in HIV-specific CD8 T cells from subjects with a viral load controlled by antiviral therapy for >2 y or from elite controllers. |
| 826 | 23772031 | Cutting edge: Prolonged exposure to HIV reinforces a poised epigenetic program for PD-1 expression in virus-specific CD8 T cells. |
| 827 | 23772031 | Ag-specific CD8 T cells play a critical role in controlling HIV infection but eventually lose antiviral functions in part because of expression and signaling through the inhibitory programmed death-1 (PD-1) receptor. |
| 828 | 23772031 | To better understand the impact of prolonged TCR ligation on regulation of PD-1 expression in HIV-specific CD8 T cells, we investigated the capacity of virus-specific CD8 T cells to modify the PD-1 epigenetic program after reduction in viral load. |
| 829 | 23772031 | We observed that the transcriptional regulatory region was unmethylated in the PD-1(hi) HIV-specific CD8 T cells, whereas it remained methylated in donor-matched naive cells at acute and chronic stages of infection. |
| 830 | 23772031 | Surprisingly, the PD-1 promoter remained unmethylated in HIV-specific CD8 T cells from subjects with a viral load controlled by antiviral therapy for >2 y or from elite controllers. |
| 831 | 23804713 | Although this vaccination induced CD4(+) CXCR5(+) PD-1(+) TFH cells in newborns, their frequency, as well as their Bcl6 expression and IL-21 and IL-4 mRNA induction, was decreased in early life. |
| 832 | 23804713 | In addition, IL-4 dampened expression of Th17-related molecules in neonatal TFH cells, as TFH cells from immunized IL-4-deficient neonates displayed enhanced expression of RORγt and IL-17. |
| 833 | 23812070 | For example, blockade of cytotoxic T-lymphocyte antigen 4 (CTLA-4) significantly improved median overall survival of melanoma patients. |
| 834 | 23812070 | Blockade of programmed cell death 1 (PD-1) or programmed cell death 1 ligand 1 (PD-L1) induced durable tumor regression and prolonged disease stabilization in patients with advanced cancers, including melanoma, non-small-cell lung cancer, and renal cell cancer. |
| 835 | 23824823 | Programmed Death 1 (PD-1) expression by human/simian immunodeficiency virus (HIV/SIV)-specific CD8 T cells has been associated with defective cytokine production and reduced in vitro proliferation capacity. |
| 836 | 23824823 | However, the cellular mechanisms that sustain PD-1(high) virus-specific CD8 T cell responses during chronic infection are unknown. |
| 837 | 23824823 | Here, we show that the PD-1(high) phenotype is associated with accelerated in vivo CD8 T cell turnover in SIV-infected rhesus macaques, especially within the SIV-specific CD8 T cell pool. |
| 838 | 23824823 | Mathematical modeling of 5-bromo-2' deoxyuridine (BrdU) labeling dynamics demonstrated a significantly increased generation rate of PD-1(high) compared to PD-1(low) CD8 T cells in all memory compartments. |
| 839 | 23824823 | Simultaneous analysis of Ki67 and BrdU kinetics revealed a complex in vivo turnover profile whereby only a small fraction of PD-1(high) cells, but virtually all PD-1(low) cells, returned to rest after activation. |
| 840 | 23824823 | Our data suggest that the persistence of PD-1(high) SIV-specific CD8 T cells in chronic infection is maintained in vivo by a mechanism involving high production coupled with a high disappearance rate. |
| 841 | 23824823 | Programmed Death 1 (PD-1) expression by human/simian immunodeficiency virus (HIV/SIV)-specific CD8 T cells has been associated with defective cytokine production and reduced in vitro proliferation capacity. |
| 842 | 23824823 | However, the cellular mechanisms that sustain PD-1(high) virus-specific CD8 T cell responses during chronic infection are unknown. |
| 843 | 23824823 | Here, we show that the PD-1(high) phenotype is associated with accelerated in vivo CD8 T cell turnover in SIV-infected rhesus macaques, especially within the SIV-specific CD8 T cell pool. |
| 844 | 23824823 | Mathematical modeling of 5-bromo-2' deoxyuridine (BrdU) labeling dynamics demonstrated a significantly increased generation rate of PD-1(high) compared to PD-1(low) CD8 T cells in all memory compartments. |
| 845 | 23824823 | Simultaneous analysis of Ki67 and BrdU kinetics revealed a complex in vivo turnover profile whereby only a small fraction of PD-1(high) cells, but virtually all PD-1(low) cells, returned to rest after activation. |
| 846 | 23824823 | Our data suggest that the persistence of PD-1(high) SIV-specific CD8 T cells in chronic infection is maintained in vivo by a mechanism involving high production coupled with a high disappearance rate. |
| 847 | 23824823 | Programmed Death 1 (PD-1) expression by human/simian immunodeficiency virus (HIV/SIV)-specific CD8 T cells has been associated with defective cytokine production and reduced in vitro proliferation capacity. |
| 848 | 23824823 | However, the cellular mechanisms that sustain PD-1(high) virus-specific CD8 T cell responses during chronic infection are unknown. |
| 849 | 23824823 | Here, we show that the PD-1(high) phenotype is associated with accelerated in vivo CD8 T cell turnover in SIV-infected rhesus macaques, especially within the SIV-specific CD8 T cell pool. |
| 850 | 23824823 | Mathematical modeling of 5-bromo-2' deoxyuridine (BrdU) labeling dynamics demonstrated a significantly increased generation rate of PD-1(high) compared to PD-1(low) CD8 T cells in all memory compartments. |
| 851 | 23824823 | Simultaneous analysis of Ki67 and BrdU kinetics revealed a complex in vivo turnover profile whereby only a small fraction of PD-1(high) cells, but virtually all PD-1(low) cells, returned to rest after activation. |
| 852 | 23824823 | Our data suggest that the persistence of PD-1(high) SIV-specific CD8 T cells in chronic infection is maintained in vivo by a mechanism involving high production coupled with a high disappearance rate. |
| 853 | 23824823 | Programmed Death 1 (PD-1) expression by human/simian immunodeficiency virus (HIV/SIV)-specific CD8 T cells has been associated with defective cytokine production and reduced in vitro proliferation capacity. |
| 854 | 23824823 | However, the cellular mechanisms that sustain PD-1(high) virus-specific CD8 T cell responses during chronic infection are unknown. |
| 855 | 23824823 | Here, we show that the PD-1(high) phenotype is associated with accelerated in vivo CD8 T cell turnover in SIV-infected rhesus macaques, especially within the SIV-specific CD8 T cell pool. |
| 856 | 23824823 | Mathematical modeling of 5-bromo-2' deoxyuridine (BrdU) labeling dynamics demonstrated a significantly increased generation rate of PD-1(high) compared to PD-1(low) CD8 T cells in all memory compartments. |
| 857 | 23824823 | Simultaneous analysis of Ki67 and BrdU kinetics revealed a complex in vivo turnover profile whereby only a small fraction of PD-1(high) cells, but virtually all PD-1(low) cells, returned to rest after activation. |
| 858 | 23824823 | Our data suggest that the persistence of PD-1(high) SIV-specific CD8 T cells in chronic infection is maintained in vivo by a mechanism involving high production coupled with a high disappearance rate. |
| 859 | 23824823 | Programmed Death 1 (PD-1) expression by human/simian immunodeficiency virus (HIV/SIV)-specific CD8 T cells has been associated with defective cytokine production and reduced in vitro proliferation capacity. |
| 860 | 23824823 | However, the cellular mechanisms that sustain PD-1(high) virus-specific CD8 T cell responses during chronic infection are unknown. |
| 861 | 23824823 | Here, we show that the PD-1(high) phenotype is associated with accelerated in vivo CD8 T cell turnover in SIV-infected rhesus macaques, especially within the SIV-specific CD8 T cell pool. |
| 862 | 23824823 | Mathematical modeling of 5-bromo-2' deoxyuridine (BrdU) labeling dynamics demonstrated a significantly increased generation rate of PD-1(high) compared to PD-1(low) CD8 T cells in all memory compartments. |
| 863 | 23824823 | Simultaneous analysis of Ki67 and BrdU kinetics revealed a complex in vivo turnover profile whereby only a small fraction of PD-1(high) cells, but virtually all PD-1(low) cells, returned to rest after activation. |
| 864 | 23824823 | Our data suggest that the persistence of PD-1(high) SIV-specific CD8 T cells in chronic infection is maintained in vivo by a mechanism involving high production coupled with a high disappearance rate. |
| 865 | 23824823 | Programmed Death 1 (PD-1) expression by human/simian immunodeficiency virus (HIV/SIV)-specific CD8 T cells has been associated with defective cytokine production and reduced in vitro proliferation capacity. |
| 866 | 23824823 | However, the cellular mechanisms that sustain PD-1(high) virus-specific CD8 T cell responses during chronic infection are unknown. |
| 867 | 23824823 | Here, we show that the PD-1(high) phenotype is associated with accelerated in vivo CD8 T cell turnover in SIV-infected rhesus macaques, especially within the SIV-specific CD8 T cell pool. |
| 868 | 23824823 | Mathematical modeling of 5-bromo-2' deoxyuridine (BrdU) labeling dynamics demonstrated a significantly increased generation rate of PD-1(high) compared to PD-1(low) CD8 T cells in all memory compartments. |
| 869 | 23824823 | Simultaneous analysis of Ki67 and BrdU kinetics revealed a complex in vivo turnover profile whereby only a small fraction of PD-1(high) cells, but virtually all PD-1(low) cells, returned to rest after activation. |
| 870 | 23824823 | Our data suggest that the persistence of PD-1(high) SIV-specific CD8 T cells in chronic infection is maintained in vivo by a mechanism involving high production coupled with a high disappearance rate. |
| 871 | 23906886 | Vacc-4x T cell responses were measured by proliferation (CFSE), INF-γ, CD107a, Granzyme B, Delayed-Type Hypersensitivity test (DTH) and cytokines and chemokines (Luminex). |
| 872 | 23906886 | At baseline, responders had higher CD8(+) T cell degranulation (p=0.05) and CD4(+) INF-γ production (p=0.01), whereas non-responders had higher production of proinflammatory TNF-α, IL-1α and IL-1ß (p<0.045) and regulatory IL-10 (p=0.07). |
| 873 | 23906886 | Notably, IL-10 and TGF-ß mediated downregulation of Vacc-4x-specific CD8(+) T cell proliferation increased only in non-responders (p<0.001). |
| 874 | 23906886 | Downregulation during the study correlated to higher PD-1 expression on Vacc-4x-specific CD8(+) T cells (r=0.44, p=0.037), but was inversely correlated to changes in Vacc4x-specific CD8(+) T cell proliferation (r=-0.52, p=0.012). |
| 875 | 23922369 | Blockade of CTLA-4 or PD1 had no effect on IFNγ production or parasite survival in SA cultures. |
| 876 | 23970300 | B7-H1 protein vaccine induces protective and therapeutic antitumor responses in SP2/0 myeloma-bearing mice. |
| 877 | 23970300 | The tumor-associated B7-H1 increases apoptosis of antigen-specific T cells through interaction with its receptor PD-1 on CD8+ T cells and contributes to tumor immune evasion. |
| 878 | 23970300 | Vaccination with this modified B7-H1 protein resulted in almost complete protection from SP2/0 tumor challenge and efficiently eliminated pre-established tumors in mice. |
| 879 | 23970300 | In addition, B7-H1 vaccination was able to decrease the percentage of CD4+ Foxp3+ regulatory T cells in tumor-bearing mice and which might improve antitumor immunity. |
| 880 | 23980172 | Hepatitis C virus (HCV) persistence is facilitated by exhaustion of CD8+ T cells that express the inhibitory receptor programmed cell death 1 (PD-1). |
| 881 | 23980172 | Control of HCV replication was associated with restoration of intrahepatic CD4+ and CD8+ T-cell immunity against multiple HCV proteins. |
| 882 | 24030473 | A defining phenotypic attribute of TFH cells is the expression of the chemokine R CXCR5, and TFH cells are typically identified by co-expression of CXCR5 together with other markers such as PD-1, ICOS, and Bcl-6. |
| 883 | 24067957 | The programmed death receptor 1 ligand/programmed death receptor 1 (PDL-1/PD-1) pathway plays an important immunoregulatory role, particularly in the context of T cell function. |
| 884 | 24067957 | Using in vitro cocultures of airway epithelial cells and T cells and in vivo models of influenza virus infection, we have demonstrated that blockade of airway epithelial PDL-1 improves CD8 T cell function, defined by increased production of gamma interferon (IFN-γ) and granzyme B and expression of CD107ab. |
| 885 | 24067957 | Our findings suggest that local manipulation of the PDL-1/PD-1 axis in the airways may represent a therapeutic alternative during acute influenza virus infection. |
| 886 | 24067957 | The programmed death receptor 1 ligand/programmed death receptor 1 (PDL-1/PD-1) pathway plays an important immunoregulatory role, particularly in the context of T cell function. |
| 887 | 24067957 | Using in vitro cocultures of airway epithelial cells and T cells and in vivo models of influenza virus infection, we have demonstrated that blockade of airway epithelial PDL-1 improves CD8 T cell function, defined by increased production of gamma interferon (IFN-γ) and granzyme B and expression of CD107ab. |
| 888 | 24067957 | Our findings suggest that local manipulation of the PDL-1/PD-1 axis in the airways may represent a therapeutic alternative during acute influenza virus infection. |
| 889 | 24114780 | Tumor-specific CD4+ T cells maintain effector and memory tumor-specific CD8+ T cells. |
| 890 | 24114780 | Here we examined whether tumor-specific CD4(+) T cells enhance CD8(+) T-cell adoptive immunotherapy in a lymphopenic environment. |
| 891 | 24114780 | Our model employed physiological doses of tyrosinase-related protein 1-specific CD4(+) transgenic T cells-CD4(+) T cells and pmel-CD8(+) T cells that when transferred individually were subtherapeutic; however, when transferred together provided significant (p ≤ 0.001) therapeutic efficacy. |
| 892 | 24114780 | When combined with CD4(+) T cells, transfer of total (naïve and effector) or effector CD8(+) T cells were highly effective, suggesting CD4(+) T cells can help mediate therapeutic effects by maintaining function of activated CD8(+) T cells. |
| 893 | 24114780 | The CD8(+) T cells recovered from mice treated with both CD8(+) and CD4(+) T cells had decreased expression of PD-1 and PD-1-blockade enhanced the therapeutic efficacy of pmel-CD8 alone, suggesting that CD4(+) T cells help reduce CD8(+) T-cell exhaustion. |
| 894 | 24114780 | These data support combining immunotherapies that elicit both tumor-specific CD4(+) and CD8(+) T cells for treatment of patients with cancer. |
| 895 | 24126533 | In contrast to the functional exhaustion of T cells observed after chronic infection, M. tuberculosis-specific CD8(+) T cells differentiated into either effector (CD127(lo) CD62L(lo)) or effector memory (CD127(hi) CD62L(lo)) cells, but not central memory cells (CD127(hi) CD62L(hi)), with low programmed death 1 (PD-1) expression, even in the presence of high levels of bacteria. |
| 896 | 24126533 | Additionally, M. tuberculosis-specific CD8(+) and CD4(+) T cells produced substantial levels of tumor necrosis factor alpha (TNF-α) and gamma interferon (IFN-γ), but not interleukin 2 (IL-2), upon in vitro restimulation. |
| 897 | 24126533 | Among M. tuberculosis-specific CD8(+) T cells, CD127(hi) effector memory cells displayed slower ongoing turnover but greater survival potential. |
| 898 | 24126533 | However, the effector function of M. tuberculosis-specific CD8(+) CD127(hi) effector memory T cells was inferior to that of canonical CD8(+) CD127(hi) memory T cells generated after acute lymphocytic choriomeningitis virus infection. |
| 899 | 24143916 | Second, non-antigen-specific immunotherapy or cancer immunomodulation is reviewed, including how monoclonal antibodies modulate the interaction between antigen-presenting cells, T-lymphocytes and tumor cells (e.g., antibodies against CTLA-4, or against PD-1 receptor or its ligands). |
| 900 | 24145857 | These cells exhibit a CXCR5(+)ICOS(hi)PD-1(hi) surface phenotype, express a high level of transcriptional repressor Bcl-6 and possess a unique ability to reside in the GC. |
| 901 | 24196313 | Recently developed unique treatment modalities are the immune checkpoint inhibitors, such as antibodies against PD-1 and PD-L1, which also show promise. |
| 902 | 24210124 | High-level T cell expression of PD-1 during SIV infection is correlated with impaired proliferation and function. |
| 903 | 24210124 | It transiently decreased expression of Ki67 and α4β7 in PBMC CD4(+) and CD8(+) Tregs for up to 8 weeks post-ART and maintained Ag-specific T-cell responses at low levels. |
| 904 | 24326266 | Enhancement of SIV-specific cell mediated immune responses by co-administration of soluble PD-1 and Tim-3 as molecular adjuvants in mice. |
| 905 | 24326266 | Since blocking the interactions between inhibitory receptors with their associated ligands using soluble PD-1 (sPD-1) and soluble Tim-3 (sTim-3) have been shown to reverse T cell exhaustion and enhance cell mediated immune responses, we tested if co-administration of sPD-1 and sTim-3 with an adenovirus vectored SIV vaccine (rAd5-SIV) can enhance cell mediated immune responses. |
| 906 | 24326266 | Furthermore, co-injection of rAd5-sPD1 and rAd5-sTim3 with rAd5-SIV in mice enhanced T cell proliferation capability and generated more antigen specific IFN-γ(+) CD4(+) and CD8(+) T cells. |
| 907 | 24326266 | Enhancement of SIV-specific cell mediated immune responses by co-administration of soluble PD-1 and Tim-3 as molecular adjuvants in mice. |
| 908 | 24326266 | Since blocking the interactions between inhibitory receptors with their associated ligands using soluble PD-1 (sPD-1) and soluble Tim-3 (sTim-3) have been shown to reverse T cell exhaustion and enhance cell mediated immune responses, we tested if co-administration of sPD-1 and sTim-3 with an adenovirus vectored SIV vaccine (rAd5-SIV) can enhance cell mediated immune responses. |
| 909 | 24326266 | Furthermore, co-injection of rAd5-sPD1 and rAd5-sTim3 with rAd5-SIV in mice enhanced T cell proliferation capability and generated more antigen specific IFN-γ(+) CD4(+) and CD8(+) T cells. |
| 910 | 24343228 | PD-1 and Tim-3 regulate the expansion of tumor antigen-specific CD8⁺ T cells induced by melanoma vaccines. |
| 911 | 24343228 | To investigate this discrepancy, we evaluated the character of vaccine-induced CD8(+) T cells with regard to the inhibitory T-cell coreceptors PD-1 and Tim-3 in patients with metastatic melanoma who were administered tumor vaccines. |
| 912 | 24343228 | Notably, the vast majority of vaccine-induced CD8(+) T cells upregulated PD-1 and a minority also upregulated Tim-3. |
| 913 | 24343228 | Levels of PD-1 and Tim-3 expression by vaccine-induced CD8(+) T cells at the time of vaccine administration correlated inversely with their expansion in vivo. |
| 914 | 24343228 | Dual blockade of PD-1 and Tim-3 enhanced the expansion and cytokine production of vaccine-induced CD8(+) T cells in vitro. |
| 915 | 24343228 | Collectively, our findings support the use of PD-1 and Tim-3 blockades with cancer vaccines to stimulate potent antitumor T-cell responses and increase the likelihood of clinical responses in patients with advanced melanoma. |
| 916 | 24343228 | PD-1 and Tim-3 regulate the expansion of tumor antigen-specific CD8⁺ T cells induced by melanoma vaccines. |
| 917 | 24343228 | To investigate this discrepancy, we evaluated the character of vaccine-induced CD8(+) T cells with regard to the inhibitory T-cell coreceptors PD-1 and Tim-3 in patients with metastatic melanoma who were administered tumor vaccines. |
| 918 | 24343228 | Notably, the vast majority of vaccine-induced CD8(+) T cells upregulated PD-1 and a minority also upregulated Tim-3. |
| 919 | 24343228 | Levels of PD-1 and Tim-3 expression by vaccine-induced CD8(+) T cells at the time of vaccine administration correlated inversely with their expansion in vivo. |
| 920 | 24343228 | Dual blockade of PD-1 and Tim-3 enhanced the expansion and cytokine production of vaccine-induced CD8(+) T cells in vitro. |
| 921 | 24343228 | Collectively, our findings support the use of PD-1 and Tim-3 blockades with cancer vaccines to stimulate potent antitumor T-cell responses and increase the likelihood of clinical responses in patients with advanced melanoma. |
| 922 | 24343228 | PD-1 and Tim-3 regulate the expansion of tumor antigen-specific CD8⁺ T cells induced by melanoma vaccines. |
| 923 | 24343228 | To investigate this discrepancy, we evaluated the character of vaccine-induced CD8(+) T cells with regard to the inhibitory T-cell coreceptors PD-1 and Tim-3 in patients with metastatic melanoma who were administered tumor vaccines. |
| 924 | 24343228 | Notably, the vast majority of vaccine-induced CD8(+) T cells upregulated PD-1 and a minority also upregulated Tim-3. |
| 925 | 24343228 | Levels of PD-1 and Tim-3 expression by vaccine-induced CD8(+) T cells at the time of vaccine administration correlated inversely with their expansion in vivo. |
| 926 | 24343228 | Dual blockade of PD-1 and Tim-3 enhanced the expansion and cytokine production of vaccine-induced CD8(+) T cells in vitro. |
| 927 | 24343228 | Collectively, our findings support the use of PD-1 and Tim-3 blockades with cancer vaccines to stimulate potent antitumor T-cell responses and increase the likelihood of clinical responses in patients with advanced melanoma. |
| 928 | 24343228 | PD-1 and Tim-3 regulate the expansion of tumor antigen-specific CD8⁺ T cells induced by melanoma vaccines. |
| 929 | 24343228 | To investigate this discrepancy, we evaluated the character of vaccine-induced CD8(+) T cells with regard to the inhibitory T-cell coreceptors PD-1 and Tim-3 in patients with metastatic melanoma who were administered tumor vaccines. |
| 930 | 24343228 | Notably, the vast majority of vaccine-induced CD8(+) T cells upregulated PD-1 and a minority also upregulated Tim-3. |
| 931 | 24343228 | Levels of PD-1 and Tim-3 expression by vaccine-induced CD8(+) T cells at the time of vaccine administration correlated inversely with their expansion in vivo. |
| 932 | 24343228 | Dual blockade of PD-1 and Tim-3 enhanced the expansion and cytokine production of vaccine-induced CD8(+) T cells in vitro. |
| 933 | 24343228 | Collectively, our findings support the use of PD-1 and Tim-3 blockades with cancer vaccines to stimulate potent antitumor T-cell responses and increase the likelihood of clinical responses in patients with advanced melanoma. |
| 934 | 24343228 | PD-1 and Tim-3 regulate the expansion of tumor antigen-specific CD8⁺ T cells induced by melanoma vaccines. |
| 935 | 24343228 | To investigate this discrepancy, we evaluated the character of vaccine-induced CD8(+) T cells with regard to the inhibitory T-cell coreceptors PD-1 and Tim-3 in patients with metastatic melanoma who were administered tumor vaccines. |
| 936 | 24343228 | Notably, the vast majority of vaccine-induced CD8(+) T cells upregulated PD-1 and a minority also upregulated Tim-3. |
| 937 | 24343228 | Levels of PD-1 and Tim-3 expression by vaccine-induced CD8(+) T cells at the time of vaccine administration correlated inversely with their expansion in vivo. |
| 938 | 24343228 | Dual blockade of PD-1 and Tim-3 enhanced the expansion and cytokine production of vaccine-induced CD8(+) T cells in vitro. |
| 939 | 24343228 | Collectively, our findings support the use of PD-1 and Tim-3 blockades with cancer vaccines to stimulate potent antitumor T-cell responses and increase the likelihood of clinical responses in patients with advanced melanoma. |
| 940 | 24343228 | PD-1 and Tim-3 regulate the expansion of tumor antigen-specific CD8⁺ T cells induced by melanoma vaccines. |
| 941 | 24343228 | To investigate this discrepancy, we evaluated the character of vaccine-induced CD8(+) T cells with regard to the inhibitory T-cell coreceptors PD-1 and Tim-3 in patients with metastatic melanoma who were administered tumor vaccines. |
| 942 | 24343228 | Notably, the vast majority of vaccine-induced CD8(+) T cells upregulated PD-1 and a minority also upregulated Tim-3. |
| 943 | 24343228 | Levels of PD-1 and Tim-3 expression by vaccine-induced CD8(+) T cells at the time of vaccine administration correlated inversely with their expansion in vivo. |
| 944 | 24343228 | Dual blockade of PD-1 and Tim-3 enhanced the expansion and cytokine production of vaccine-induced CD8(+) T cells in vitro. |
| 945 | 24343228 | Collectively, our findings support the use of PD-1 and Tim-3 blockades with cancer vaccines to stimulate potent antitumor T-cell responses and increase the likelihood of clinical responses in patients with advanced melanoma. |
| 946 | 24391505 | Hepatitis B virus (HBV) persistence is facilitated by exhaustion of CD8 T cells that express the inhibitory receptor programmed cell death-1 (PD-1). |
| 947 | 24391505 | Improvement of the HBV-specific T cell function has been obtained in vitro by inhibiting the PD-1/PD-ligand 1 (PD-L1) interaction. |
| 948 | 24391505 | We could show that PD-1 expression on CD8 T cells was correlated with WHV viral loads during WHV infection. |
| 949 | 24391505 | ETV treatment significantly decreased PD-1 expression on CD8 T cells in chronic carriers. |
| 950 | 24391505 | In vivo blockade of PD-1/PD-L1 pathway on CD8 T cells, in combination with ETV treatment and DNA vaccination, potently enhanced the function of virus-specific T cells. |
| 951 | 24391505 | Hepatitis B virus (HBV) persistence is facilitated by exhaustion of CD8 T cells that express the inhibitory receptor programmed cell death-1 (PD-1). |
| 952 | 24391505 | Improvement of the HBV-specific T cell function has been obtained in vitro by inhibiting the PD-1/PD-ligand 1 (PD-L1) interaction. |
| 953 | 24391505 | We could show that PD-1 expression on CD8 T cells was correlated with WHV viral loads during WHV infection. |
| 954 | 24391505 | ETV treatment significantly decreased PD-1 expression on CD8 T cells in chronic carriers. |
| 955 | 24391505 | In vivo blockade of PD-1/PD-L1 pathway on CD8 T cells, in combination with ETV treatment and DNA vaccination, potently enhanced the function of virus-specific T cells. |
| 956 | 24391505 | Hepatitis B virus (HBV) persistence is facilitated by exhaustion of CD8 T cells that express the inhibitory receptor programmed cell death-1 (PD-1). |
| 957 | 24391505 | Improvement of the HBV-specific T cell function has been obtained in vitro by inhibiting the PD-1/PD-ligand 1 (PD-L1) interaction. |
| 958 | 24391505 | We could show that PD-1 expression on CD8 T cells was correlated with WHV viral loads during WHV infection. |
| 959 | 24391505 | ETV treatment significantly decreased PD-1 expression on CD8 T cells in chronic carriers. |
| 960 | 24391505 | In vivo blockade of PD-1/PD-L1 pathway on CD8 T cells, in combination with ETV treatment and DNA vaccination, potently enhanced the function of virus-specific T cells. |
| 961 | 24391505 | Hepatitis B virus (HBV) persistence is facilitated by exhaustion of CD8 T cells that express the inhibitory receptor programmed cell death-1 (PD-1). |
| 962 | 24391505 | Improvement of the HBV-specific T cell function has been obtained in vitro by inhibiting the PD-1/PD-ligand 1 (PD-L1) interaction. |
| 963 | 24391505 | We could show that PD-1 expression on CD8 T cells was correlated with WHV viral loads during WHV infection. |
| 964 | 24391505 | ETV treatment significantly decreased PD-1 expression on CD8 T cells in chronic carriers. |
| 965 | 24391505 | In vivo blockade of PD-1/PD-L1 pathway on CD8 T cells, in combination with ETV treatment and DNA vaccination, potently enhanced the function of virus-specific T cells. |
| 966 | 24391505 | Hepatitis B virus (HBV) persistence is facilitated by exhaustion of CD8 T cells that express the inhibitory receptor programmed cell death-1 (PD-1). |
| 967 | 24391505 | Improvement of the HBV-specific T cell function has been obtained in vitro by inhibiting the PD-1/PD-ligand 1 (PD-L1) interaction. |
| 968 | 24391505 | We could show that PD-1 expression on CD8 T cells was correlated with WHV viral loads during WHV infection. |
| 969 | 24391505 | ETV treatment significantly decreased PD-1 expression on CD8 T cells in chronic carriers. |
| 970 | 24391505 | In vivo blockade of PD-1/PD-L1 pathway on CD8 T cells, in combination with ETV treatment and DNA vaccination, potently enhanced the function of virus-specific T cells. |
| 971 | 24391639 | Here we studied the expression of eight different iRs by CD8 T cells of healthy humans, including CTLA-4, PD1, TIM3, LAG3, 2B4, BTLA, CD160, and KLRG1. |
| 972 | 24404420 | We have recently reported that the PD-1 and CTLA4 signaling pathways are active in both effector and regulatory T cells, causing profound immune dysfunctions in the tumor microenvironment. |
| 973 | 24408920 | Dual blockade of PD-1 and CTLA-4 combined with tumor vaccine effectively restores T-cell rejection function in tumors--response. |
| 974 | 24408925 | Dual blockade of PD-1 and CTLA-4 combined with tumor vaccine effectively restores T-cell rejection function in tumors--letter. |
| 975 | 24455752 | We investigated how to rescue CD8(+) T cell function in long-established immunogenic melanomas that contained a high percentage of endogenous PD-1(+) tumor-specific CD8(+) T cells that were dysfunctional. |
| 976 | 24455752 | Following treatment with antigen-producing A1-R, the majority of tumor-specific CD8(+) T cells still expressed a high level of PD-1 in the tumor. |
| 977 | 24455752 | We investigated how to rescue CD8(+) T cell function in long-established immunogenic melanomas that contained a high percentage of endogenous PD-1(+) tumor-specific CD8(+) T cells that were dysfunctional. |
| 978 | 24455752 | Following treatment with antigen-producing A1-R, the majority of tumor-specific CD8(+) T cells still expressed a high level of PD-1 in the tumor. |
| 979 | 24462405 | Vaccination with Leishmania mexicana LPG induces PD-1 in CD8⁺ and PD-L2 in macrophages thereby suppressing the immune response: a model to assess vaccine efficacy. |
| 980 | 24462405 | Since unsuccessful protection could be related to suppressed T cell responses, we analyzed the expression of inhibitory receptor PD-1 in CD8(+) and CD4(+) lymphocytes and it is ligand PD-L2 in macrophages of BALB/c mice immunized with various doses of Leishmania mexicana LPG and re-stimulated in vitro with different concentrations of LPG. |
| 981 | 24462405 | The expression of PD-1, PD-L2 and CD137 is modulated according to the amount of LPG used during immunization and in vitro re-stimulation. |
| 982 | 24462405 | Infection with 1×10(5) parasites increased the PD-1 expression in CD8(+) and diminished PD-L2 in macrophages. |
| 983 | 24462405 | We propose that the analysis of PD-1 and PD-L2 are useful tools to monitor the optimal dose for vaccination candidates. |
| 984 | 24462405 | Vaccination with Leishmania mexicana LPG induces PD-1 in CD8⁺ and PD-L2 in macrophages thereby suppressing the immune response: a model to assess vaccine efficacy. |
| 985 | 24462405 | Since unsuccessful protection could be related to suppressed T cell responses, we analyzed the expression of inhibitory receptor PD-1 in CD8(+) and CD4(+) lymphocytes and it is ligand PD-L2 in macrophages of BALB/c mice immunized with various doses of Leishmania mexicana LPG and re-stimulated in vitro with different concentrations of LPG. |
| 986 | 24462405 | The expression of PD-1, PD-L2 and CD137 is modulated according to the amount of LPG used during immunization and in vitro re-stimulation. |
| 987 | 24462405 | Infection with 1×10(5) parasites increased the PD-1 expression in CD8(+) and diminished PD-L2 in macrophages. |
| 988 | 24462405 | We propose that the analysis of PD-1 and PD-L2 are useful tools to monitor the optimal dose for vaccination candidates. |
| 989 | 24462405 | Vaccination with Leishmania mexicana LPG induces PD-1 in CD8⁺ and PD-L2 in macrophages thereby suppressing the immune response: a model to assess vaccine efficacy. |
| 990 | 24462405 | Since unsuccessful protection could be related to suppressed T cell responses, we analyzed the expression of inhibitory receptor PD-1 in CD8(+) and CD4(+) lymphocytes and it is ligand PD-L2 in macrophages of BALB/c mice immunized with various doses of Leishmania mexicana LPG and re-stimulated in vitro with different concentrations of LPG. |
| 991 | 24462405 | The expression of PD-1, PD-L2 and CD137 is modulated according to the amount of LPG used during immunization and in vitro re-stimulation. |
| 992 | 24462405 | Infection with 1×10(5) parasites increased the PD-1 expression in CD8(+) and diminished PD-L2 in macrophages. |
| 993 | 24462405 | We propose that the analysis of PD-1 and PD-L2 are useful tools to monitor the optimal dose for vaccination candidates. |
| 994 | 24462405 | Vaccination with Leishmania mexicana LPG induces PD-1 in CD8⁺ and PD-L2 in macrophages thereby suppressing the immune response: a model to assess vaccine efficacy. |
| 995 | 24462405 | Since unsuccessful protection could be related to suppressed T cell responses, we analyzed the expression of inhibitory receptor PD-1 in CD8(+) and CD4(+) lymphocytes and it is ligand PD-L2 in macrophages of BALB/c mice immunized with various doses of Leishmania mexicana LPG and re-stimulated in vitro with different concentrations of LPG. |
| 996 | 24462405 | The expression of PD-1, PD-L2 and CD137 is modulated according to the amount of LPG used during immunization and in vitro re-stimulation. |
| 997 | 24462405 | Infection with 1×10(5) parasites increased the PD-1 expression in CD8(+) and diminished PD-L2 in macrophages. |
| 998 | 24462405 | We propose that the analysis of PD-1 and PD-L2 are useful tools to monitor the optimal dose for vaccination candidates. |
| 999 | 24462405 | Vaccination with Leishmania mexicana LPG induces PD-1 in CD8⁺ and PD-L2 in macrophages thereby suppressing the immune response: a model to assess vaccine efficacy. |
| 1000 | 24462405 | Since unsuccessful protection could be related to suppressed T cell responses, we analyzed the expression of inhibitory receptor PD-1 in CD8(+) and CD4(+) lymphocytes and it is ligand PD-L2 in macrophages of BALB/c mice immunized with various doses of Leishmania mexicana LPG and re-stimulated in vitro with different concentrations of LPG. |
| 1001 | 24462405 | The expression of PD-1, PD-L2 and CD137 is modulated according to the amount of LPG used during immunization and in vitro re-stimulation. |
| 1002 | 24462405 | Infection with 1×10(5) parasites increased the PD-1 expression in CD8(+) and diminished PD-L2 in macrophages. |
| 1003 | 24462405 | We propose that the analysis of PD-1 and PD-L2 are useful tools to monitor the optimal dose for vaccination candidates. |
| 1004 | 24477411 | Indeed, drugs blocking the inhibitory signal generated by the engagement of cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death-1 (PD-1) found on T-cells has emerged as potent means to combat the immunosuppressive milieu. |
| 1005 | 24497824 | In co-culture experiments we confirmed CXCR5+ cells from HIV-uninfected donors provide help to B cells and more specifically, we identified a CCR7(high)CXCR5(high)CCR6(high)PD-1(high) CD4 T cell population that secretes IL-21 and enhances isotype-switched immunoglobulin production. |
| 1006 | 24509171 | NY-ESO-1 CD4 and CD8 T-cell responses were elicited in these patients and their epitopes were identified. |
| 1007 | 24509171 | Using a multifunctional cytokine assay, the number of single or double cytokine-producing cells was increased in NY-ESO-1-specific CD4 and CD8 T cells after vaccination. |
| 1008 | 24509171 | Multiple cytokine-producing cells were observed in PD-1 (-) and PD-1 (+) CD4 T cells. |
| 1009 | 24509171 | In conclusion, our study indicated that the NY-ESO-1 OLP vaccine mixed with Picibanil OK-432 and Montanide ISA-51 was well tolerated and elicited NY-ESO-1-specific humoral and CD4 and CD8 T-cell responses in immunized patients. |
| 1010 | 24514956 | There were trends toward associations for longer OS and certain immune cell subsets before immunotherapy: lower PD-1(+)Tim-3(NEG)CD4EM (P = 0.005, adjusted P = 0.010), higher PD-1(NEG)Tim-3(+)CD8 (P = 0.002, adjusted P = 0.004), and a higher number of CTLA-4(NEG) Tregs (P = 0.005, adjusted P = 0.010). |
| 1011 | 24574499 | In chronic infection, dominant epitope-specific T cells developed a terminal differentiated KLRG1(+)/PD-1(lo) surface phenotype that was significantly reduced in the cryptic epitope-specific T cell populations. |
| 1012 | 24574499 | In contrast, cryptic epitope-specific CD4 T cells maintained significantly greater IFN-γ(+)TNF-α(+)IL-2(+) and TNF-α(+)IL-2(+) memory-associated polyfunctionality and enhanced proliferative capacity. |
| 1013 | 24574499 | Vaccine-associated IL-17A production by cryptic CD4 T cells was also enhanced, but without increased neutrophilia/pathology. |
| 1014 | 24590765 | Blimp-1 represses CD8 T cell expression of PD-1 using a feed-forward transcriptional circuit during acute viral infection. |
| 1015 | 24590765 | We show here that B lymphocyte-induced maturation protein 1 (Blimp-1)-deficient CD8 T cells fail to repress PD-1 during the early stages of CD8 T cell differentiation after acute infection with lymphocytic choriomeningitis virus (LCMV) strain Armstrong. |
| 1016 | 24590765 | Blimp-1 represses PD-1 through a feed-forward repressive circuit by regulating PD-1 directly and by repressing NFATc1 expression, an activator of PD-1 expression. |
| 1017 | 24590765 | Blimp-1 binding induces a repressive chromatin structure at the PD-1 locus, leading to the eviction of NFATc1 from its site. |
| 1018 | 24590765 | These data place Blimp-1 at an important phase of the CD8 T cell effector response and provide a molecular mechanism for its repression of PD-1. |
| 1019 | 24590765 | Blimp-1 represses CD8 T cell expression of PD-1 using a feed-forward transcriptional circuit during acute viral infection. |
| 1020 | 24590765 | We show here that B lymphocyte-induced maturation protein 1 (Blimp-1)-deficient CD8 T cells fail to repress PD-1 during the early stages of CD8 T cell differentiation after acute infection with lymphocytic choriomeningitis virus (LCMV) strain Armstrong. |
| 1021 | 24590765 | Blimp-1 represses PD-1 through a feed-forward repressive circuit by regulating PD-1 directly and by repressing NFATc1 expression, an activator of PD-1 expression. |
| 1022 | 24590765 | Blimp-1 binding induces a repressive chromatin structure at the PD-1 locus, leading to the eviction of NFATc1 from its site. |
| 1023 | 24590765 | These data place Blimp-1 at an important phase of the CD8 T cell effector response and provide a molecular mechanism for its repression of PD-1. |
| 1024 | 24590765 | Blimp-1 represses CD8 T cell expression of PD-1 using a feed-forward transcriptional circuit during acute viral infection. |
| 1025 | 24590765 | We show here that B lymphocyte-induced maturation protein 1 (Blimp-1)-deficient CD8 T cells fail to repress PD-1 during the early stages of CD8 T cell differentiation after acute infection with lymphocytic choriomeningitis virus (LCMV) strain Armstrong. |
| 1026 | 24590765 | Blimp-1 represses PD-1 through a feed-forward repressive circuit by regulating PD-1 directly and by repressing NFATc1 expression, an activator of PD-1 expression. |
| 1027 | 24590765 | Blimp-1 binding induces a repressive chromatin structure at the PD-1 locus, leading to the eviction of NFATc1 from its site. |
| 1028 | 24590765 | These data place Blimp-1 at an important phase of the CD8 T cell effector response and provide a molecular mechanism for its repression of PD-1. |
| 1029 | 24590765 | Blimp-1 represses CD8 T cell expression of PD-1 using a feed-forward transcriptional circuit during acute viral infection. |
| 1030 | 24590765 | We show here that B lymphocyte-induced maturation protein 1 (Blimp-1)-deficient CD8 T cells fail to repress PD-1 during the early stages of CD8 T cell differentiation after acute infection with lymphocytic choriomeningitis virus (LCMV) strain Armstrong. |
| 1031 | 24590765 | Blimp-1 represses PD-1 through a feed-forward repressive circuit by regulating PD-1 directly and by repressing NFATc1 expression, an activator of PD-1 expression. |
| 1032 | 24590765 | Blimp-1 binding induces a repressive chromatin structure at the PD-1 locus, leading to the eviction of NFATc1 from its site. |
| 1033 | 24590765 | These data place Blimp-1 at an important phase of the CD8 T cell effector response and provide a molecular mechanism for its repression of PD-1. |
| 1034 | 24590765 | Blimp-1 represses CD8 T cell expression of PD-1 using a feed-forward transcriptional circuit during acute viral infection. |
| 1035 | 24590765 | We show here that B lymphocyte-induced maturation protein 1 (Blimp-1)-deficient CD8 T cells fail to repress PD-1 during the early stages of CD8 T cell differentiation after acute infection with lymphocytic choriomeningitis virus (LCMV) strain Armstrong. |
| 1036 | 24590765 | Blimp-1 represses PD-1 through a feed-forward repressive circuit by regulating PD-1 directly and by repressing NFATc1 expression, an activator of PD-1 expression. |
| 1037 | 24590765 | Blimp-1 binding induces a repressive chromatin structure at the PD-1 locus, leading to the eviction of NFATc1 from its site. |
| 1038 | 24590765 | These data place Blimp-1 at an important phase of the CD8 T cell effector response and provide a molecular mechanism for its repression of PD-1. |
| 1039 | 24598447 | Fusion protein of mutant B7-DC and Fc enhances the antitumor immune effect of GM-CSF-secreting whole-cell vaccine. |
| 1040 | 24598447 | In addition to its coinhibitory receptor, programmed death receptor 1 (PD-1), evidence suggests that B7-DC interacts with an unidentified costimulatory receptor on T cells. |
| 1041 | 24598447 | B7-DC mutants with selective binding capacity for the costimulatory receptor may be effective in stimulating antitumor immune responses, while avoiding the inhibitory effects of PD-1. |
| 1042 | 24598447 | In this study, we concomitantly administered a GM-CSF-secreting whole-cell vaccine together with a fusion protein of mutant B7-DC and Fc portion (mB7-DC-Fc), which binds selectively to the costimulatory receptor. |
| 1043 | 24598447 | In addition, mB7-DC-Fc increased IFN-γ and IL-2 production and decreased IL-4 and IL-10 production in vitro, indicating that mB7-DC-Fc tips the Th1/Th2 balance toward Th1 dominance, which is more favorable for antitumor immunity. |
| 1044 | 24598447 | Furthermore, mB7-DC-Fc decreased the PD-1(+) proportion of CD8(+) T cells in vitro and tumor-infiltrating CD8(+) T cells in vivo, suggesting that mB7-DC-Fc may maintain tumor-infiltrating CD8(+) T cells in a nonexhausted state. |
| 1045 | 24598447 | Fusion protein of mutant B7-DC and Fc enhances the antitumor immune effect of GM-CSF-secreting whole-cell vaccine. |
| 1046 | 24598447 | In addition to its coinhibitory receptor, programmed death receptor 1 (PD-1), evidence suggests that B7-DC interacts with an unidentified costimulatory receptor on T cells. |
| 1047 | 24598447 | B7-DC mutants with selective binding capacity for the costimulatory receptor may be effective in stimulating antitumor immune responses, while avoiding the inhibitory effects of PD-1. |
| 1048 | 24598447 | In this study, we concomitantly administered a GM-CSF-secreting whole-cell vaccine together with a fusion protein of mutant B7-DC and Fc portion (mB7-DC-Fc), which binds selectively to the costimulatory receptor. |
| 1049 | 24598447 | In addition, mB7-DC-Fc increased IFN-γ and IL-2 production and decreased IL-4 and IL-10 production in vitro, indicating that mB7-DC-Fc tips the Th1/Th2 balance toward Th1 dominance, which is more favorable for antitumor immunity. |
| 1050 | 24598447 | Furthermore, mB7-DC-Fc decreased the PD-1(+) proportion of CD8(+) T cells in vitro and tumor-infiltrating CD8(+) T cells in vivo, suggesting that mB7-DC-Fc may maintain tumor-infiltrating CD8(+) T cells in a nonexhausted state. |
| 1051 | 24598447 | Fusion protein of mutant B7-DC and Fc enhances the antitumor immune effect of GM-CSF-secreting whole-cell vaccine. |
| 1052 | 24598447 | In addition to its coinhibitory receptor, programmed death receptor 1 (PD-1), evidence suggests that B7-DC interacts with an unidentified costimulatory receptor on T cells. |
| 1053 | 24598447 | B7-DC mutants with selective binding capacity for the costimulatory receptor may be effective in stimulating antitumor immune responses, while avoiding the inhibitory effects of PD-1. |
| 1054 | 24598447 | In this study, we concomitantly administered a GM-CSF-secreting whole-cell vaccine together with a fusion protein of mutant B7-DC and Fc portion (mB7-DC-Fc), which binds selectively to the costimulatory receptor. |
| 1055 | 24598447 | In addition, mB7-DC-Fc increased IFN-γ and IL-2 production and decreased IL-4 and IL-10 production in vitro, indicating that mB7-DC-Fc tips the Th1/Th2 balance toward Th1 dominance, which is more favorable for antitumor immunity. |
| 1056 | 24598447 | Furthermore, mB7-DC-Fc decreased the PD-1(+) proportion of CD8(+) T cells in vitro and tumor-infiltrating CD8(+) T cells in vivo, suggesting that mB7-DC-Fc may maintain tumor-infiltrating CD8(+) T cells in a nonexhausted state. |
| 1057 | 24605077 | TFH cells are characterized by their expression of master regulator, Bcl-6, and chemokine receptor, CXCR5, which are essential for the migration of T cells into the B cell follicle. |
| 1058 | 24605077 | IL-6 and IL-21 cytokine-mediated STAT signaling pathways, including STAT1 and STAT3, are crucial for inducing Bcl-6 expression and TFH cell differentiation. |
| 1059 | 24605077 | TFH cells express important surface molecules such as ICOS, PD-1, IL-21, BTLA, SAP and CD40L for mediating the interaction between T and B cells. |
| 1060 | 24605077 | The miR-17-92 cluster induces Bcl-6 and TFH cell differentiation, whereas miR-10a negatively regulates Bcl-6 expression in T cells. |
| 1061 | 24605077 | In addition, follicular regulatory T (TFR) cells are studied as thymus-derived CXCR5(+)PD-1(+)Foxp3(+) Treg cells that play a significant role in limiting the GC response. |
| 1062 | 24605077 | TFH cells are characterized by their expression of master regulator, Bcl-6, and chemokine receptor, CXCR5, which are essential for the migration of T cells into the B cell follicle. |
| 1063 | 24605077 | IL-6 and IL-21 cytokine-mediated STAT signaling pathways, including STAT1 and STAT3, are crucial for inducing Bcl-6 expression and TFH cell differentiation. |
| 1064 | 24605077 | TFH cells express important surface molecules such as ICOS, PD-1, IL-21, BTLA, SAP and CD40L for mediating the interaction between T and B cells. |
| 1065 | 24605077 | The miR-17-92 cluster induces Bcl-6 and TFH cell differentiation, whereas miR-10a negatively regulates Bcl-6 expression in T cells. |
| 1066 | 24605077 | In addition, follicular regulatory T (TFR) cells are studied as thymus-derived CXCR5(+)PD-1(+)Foxp3(+) Treg cells that play a significant role in limiting the GC response. |
| 1067 | 24642562 | We analyzed the expression of Tim-3 and PD-1, two recently identified T cell negative immune checkpoint receptors, over the course of WNV infection. |
| 1068 | 24642562 | Symptomatic WNV+ donors exhibited higher frequencies of Tim-3+ cells than asymptomatic subjects within naïve/early differentiated CD28+/-CD57-CD4+ and differentiated CD28-CD57-CD8+ T cells. |
| 1069 | 24658839 | In an attempt to shed more light on the immunosuppressive environment in uterine tumors, we analyzed the presence of PD-L1, PDL2, B7-H4, indoleamine 2,3-dioxygenase (IDO), galectin- 1, galectin-3, arginase-1 activity and myeloid-derived suppressor cell (MDSC) infiltration. |
| 1070 | 24658839 | IDO, PD-L1, PD-L2 and B7-H4 were analyzed by immunohistochemistry. |
| 1071 | 24658839 | For PD-L1 and B7-H4, we found high expression in 92 and 90 % of endometrial cancers, respectively, and in 100 and 92 % of the sarcomas. |
| 1072 | 24658839 | These results indicate that the PD-1/PD-L1 interaction and B7-H4 could be possible targets for immune intervention in uterine cancer patients as well as mediation of MDSC function. |
| 1073 | 24706270 | Concerning this point, the recent studies suggest the concept of immune exhaustion of CD8 T cells, characterized by their decreased production of IL-2, TNFα, and IFNγ even after antigen stimulation. |
| 1074 | 24706270 | The identification of immune effector and/or exhausted CD8 T cells by monitoring multiple parameters including T cell exhaustion markers such as PD-1 and Tim-3 and intracellular cytokines is, therefore, crucial to understand the real-time, ongoing immune status. |
| 1075 | 24706270 | By stimulation of PBMCs with PMA/ionomycin for 6 h, more than 1-2 % of total CD8 T cells are identified as positive in terms of multifunctionality, thus producing multiple cytokines--IL-2, TNFα, and IFNγ--at single-cell level in case of all healthy donors. |
| 1076 | 24728077 | PD-1/B7-H1 is an important inhibitory axis in the tumor microenvironment. |
| 1077 | 24728077 | We observed that using anti-PD-1 antibody and a multipeptide vaccine (consisting of immunogenic peptides derived from breast cancer antigens, neu, legumain, and β-catenin) as a combination therapy regimen for the treatment of breast cancer-bearing mice prolonged the vaccine-induced progression-free survival period. |
| 1078 | 24728077 | This prolonged survival was associated with increase in number of Tc1 and Tc2 CD8 T cells with memory precursor phenotype, CD27+IL-7RhiT-betlo, and decrease in number of PD-1+ dendritic cells (DC) in regressing tumors and enhanced antigen reactivity of tumor-infiltrating CD8 T cells. |
| 1079 | 24728077 | It was also observed that blockade of PD-1 on tumor DCs enhanced IL-7R expression on CD8 T cells. |
| 1080 | 24728077 | Taken together, our results suggest that PD-1 blockade enhances breast cancer vaccine efficacy by altering both CD8 T cell and DC components of the tumor microenvironment. |
| 1081 | 24728077 | PD-1/B7-H1 is an important inhibitory axis in the tumor microenvironment. |
| 1082 | 24728077 | We observed that using anti-PD-1 antibody and a multipeptide vaccine (consisting of immunogenic peptides derived from breast cancer antigens, neu, legumain, and β-catenin) as a combination therapy regimen for the treatment of breast cancer-bearing mice prolonged the vaccine-induced progression-free survival period. |
| 1083 | 24728077 | This prolonged survival was associated with increase in number of Tc1 and Tc2 CD8 T cells with memory precursor phenotype, CD27+IL-7RhiT-betlo, and decrease in number of PD-1+ dendritic cells (DC) in regressing tumors and enhanced antigen reactivity of tumor-infiltrating CD8 T cells. |
| 1084 | 24728077 | It was also observed that blockade of PD-1 on tumor DCs enhanced IL-7R expression on CD8 T cells. |
| 1085 | 24728077 | Taken together, our results suggest that PD-1 blockade enhances breast cancer vaccine efficacy by altering both CD8 T cell and DC components of the tumor microenvironment. |
| 1086 | 24728077 | PD-1/B7-H1 is an important inhibitory axis in the tumor microenvironment. |
| 1087 | 24728077 | We observed that using anti-PD-1 antibody and a multipeptide vaccine (consisting of immunogenic peptides derived from breast cancer antigens, neu, legumain, and β-catenin) as a combination therapy regimen for the treatment of breast cancer-bearing mice prolonged the vaccine-induced progression-free survival period. |
| 1088 | 24728077 | This prolonged survival was associated with increase in number of Tc1 and Tc2 CD8 T cells with memory precursor phenotype, CD27+IL-7RhiT-betlo, and decrease in number of PD-1+ dendritic cells (DC) in regressing tumors and enhanced antigen reactivity of tumor-infiltrating CD8 T cells. |
| 1089 | 24728077 | It was also observed that blockade of PD-1 on tumor DCs enhanced IL-7R expression on CD8 T cells. |
| 1090 | 24728077 | Taken together, our results suggest that PD-1 blockade enhances breast cancer vaccine efficacy by altering both CD8 T cell and DC components of the tumor microenvironment. |
| 1091 | 24728077 | PD-1/B7-H1 is an important inhibitory axis in the tumor microenvironment. |
| 1092 | 24728077 | We observed that using anti-PD-1 antibody and a multipeptide vaccine (consisting of immunogenic peptides derived from breast cancer antigens, neu, legumain, and β-catenin) as a combination therapy regimen for the treatment of breast cancer-bearing mice prolonged the vaccine-induced progression-free survival period. |
| 1093 | 24728077 | This prolonged survival was associated with increase in number of Tc1 and Tc2 CD8 T cells with memory precursor phenotype, CD27+IL-7RhiT-betlo, and decrease in number of PD-1+ dendritic cells (DC) in regressing tumors and enhanced antigen reactivity of tumor-infiltrating CD8 T cells. |
| 1094 | 24728077 | It was also observed that blockade of PD-1 on tumor DCs enhanced IL-7R expression on CD8 T cells. |
| 1095 | 24728077 | Taken together, our results suggest that PD-1 blockade enhances breast cancer vaccine efficacy by altering both CD8 T cell and DC components of the tumor microenvironment. |
| 1096 | 24741623 | In addition, programmed death-1 (PD-1)/killer cell lectin-like receptor G1 (KLRG-1) double positive cells were found only in treated patients and not in those with active TB. |
| 1097 | 24771328 | High levels of peripheral blood Tregs prior to therapy were associated with decreased progression-free survival in FL patients treated with either chemotherapy or combination immunotherapy that targeted CD20 and PD-1 with monoclonal antibodies rituximab and pidilizumab, respectively. |
| 1098 | 24788575 | The management of high-risk melanoma has historically included primary surgical resection with or without lymphadenectomy followed by an array of adjuvant options including radiation therapy or immunomodulatory therapies such as interferon-α, granulocyte macrophage colony-stimulating factor, and a multitude of vaccines. |
| 1099 | 24788575 | While the role of vaccines in the adjuvant setting of high-risk melanoma presently remains unclear, recent advances in immunotherapy for melanoma including development of cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death 1 (PD-1) monoclonal antibodies have demonstrated meaningful clinical responses. |
| 1100 | 24795357 | We have shown that a vaccine based on alphavirus replicon particles (VRP) activates strong cellular and humoral immunity to tyrosinase-related protein-2 (TRP2) melanoma antigen, providing prophylactic and therapeutic effects in stringent mouse models. |
| 1101 | 24795357 | Here, we report that the immunogenicity and efficacy of this vaccine is increased in combination with either antagonist anti-CTL antigen-4 (CTLA-4) or agonist anti-glucocorticoid-induced TNF family-related gene (GITR) immunomodulatory monoclonal antibodies (mAb). |
| 1102 | 24795357 | These mAbs had similar adjuvant effects in priming an adaptive immune response against the vaccine-encoded antigen, augmenting, respectively, approximately 4- and 2-fold the TRP2-specific CD8(+) T-cell response and circulating Abs, compared with the vaccine alone. |
| 1103 | 24795357 | Furthermore, while both mAbs increased the frequency of tumor-infiltrating CD8(+) T cells, anti-CTLA-4 mAb also increased the quantity of intratumor CD4(+)Foxp3(-) T cells expressing the negative costimulatory molecule programmed death-1 (PD-1). |
| 1104 | 24795357 | They also indicate that tumor-infiltrating CD4(+)Foxp3(-)PD-1(+) T cells may affect the outcome of immunomodulatory treatments. |
| 1105 | 24795357 | We have shown that a vaccine based on alphavirus replicon particles (VRP) activates strong cellular and humoral immunity to tyrosinase-related protein-2 (TRP2) melanoma antigen, providing prophylactic and therapeutic effects in stringent mouse models. |
| 1106 | 24795357 | Here, we report that the immunogenicity and efficacy of this vaccine is increased in combination with either antagonist anti-CTL antigen-4 (CTLA-4) or agonist anti-glucocorticoid-induced TNF family-related gene (GITR) immunomodulatory monoclonal antibodies (mAb). |
| 1107 | 24795357 | These mAbs had similar adjuvant effects in priming an adaptive immune response against the vaccine-encoded antigen, augmenting, respectively, approximately 4- and 2-fold the TRP2-specific CD8(+) T-cell response and circulating Abs, compared with the vaccine alone. |
| 1108 | 24795357 | Furthermore, while both mAbs increased the frequency of tumor-infiltrating CD8(+) T cells, anti-CTLA-4 mAb also increased the quantity of intratumor CD4(+)Foxp3(-) T cells expressing the negative costimulatory molecule programmed death-1 (PD-1). |
| 1109 | 24795357 | They also indicate that tumor-infiltrating CD4(+)Foxp3(-)PD-1(+) T cells may affect the outcome of immunomodulatory treatments. |
| 1110 | 24807710 | The expansion of the CD8α(-) subpopulation of DCs through injection of WT mice with granulocyte-macrophage colony-stimulating factor (GM-CSF) DNA reduced the amount of latency and PD-1 expression in the TG of infected mice. |
| 1111 | 24812273 | In support of this likelihood, PDL1 upregulation in this setting relied upon IFNγ-expressing tumor-infiltrating CD4(+) and CD8(+) T cells and administration of a PD1-blocking antibody with TEGVAX elicited complete regression of established tumors. |
| 1112 | 24857059 | Recent introduction of immune modulators of cytotoxic T-lymphocyte antigen (CTLA)-4 and programmed cell death 1/programmed cell death 1 ligand (PD-1/PDL1) add much excitement to this field. |
| 1113 | 24892254 | Of particular interest are agents that inhibit the interaction between the programmed death-1 (PD-1) receptor and its ligand (PD-L1) at the T-cell/antigen-presenting cell interface. |
| 1114 | 24892254 | Monoclonal antibodies to PD-1 (eg, nivolumab, lambrolizumab, and pidilizumab) and PD-L1 (MPDL3280A and BMS-936559) are in various stages of clinical development. |
| 1115 | 24892254 | The clinical trajectory of these agents is discussed herein, with specific attention to the potential placement of PD-1/ PD-L1 inhibition in the crowded therapeutic landscape of mRCC. |
| 1116 | 24892254 | Of particular interest are agents that inhibit the interaction between the programmed death-1 (PD-1) receptor and its ligand (PD-L1) at the T-cell/antigen-presenting cell interface. |
| 1117 | 24892254 | Monoclonal antibodies to PD-1 (eg, nivolumab, lambrolizumab, and pidilizumab) and PD-L1 (MPDL3280A and BMS-936559) are in various stages of clinical development. |
| 1118 | 24892254 | The clinical trajectory of these agents is discussed herein, with specific attention to the potential placement of PD-1/ PD-L1 inhibition in the crowded therapeutic landscape of mRCC. |
| 1119 | 24892254 | Of particular interest are agents that inhibit the interaction between the programmed death-1 (PD-1) receptor and its ligand (PD-L1) at the T-cell/antigen-presenting cell interface. |
| 1120 | 24892254 | Monoclonal antibodies to PD-1 (eg, nivolumab, lambrolizumab, and pidilizumab) and PD-L1 (MPDL3280A and BMS-936559) are in various stages of clinical development. |
| 1121 | 24892254 | The clinical trajectory of these agents is discussed herein, with specific attention to the potential placement of PD-1/ PD-L1 inhibition in the crowded therapeutic landscape of mRCC. |
| 1122 | 24894091 | Immunohistochemical data of infiltrating (suppressive) cells, such as T cells, regulatory T cells, myeloid-derived suppressor cells, and mast cells, or the expression of T-cell inhibitory factors (PD-1/PD-L1, IDO, and galectins), cytotoxic molecules (granzyme-B), melanocyte differentiation antigens, HLA class-I and tolerogenic cytokines [interleukin (IL)-1, IL-6, IL-10, TNF-α, and TGF-β] were correlated statistically to clinical outcome and overall survival (OS). |
| 1123 | 24894091 | Significantly more tumor-infiltrating CD4(+) and CD8(+) T cells (both P < 0.05) were found in nonprogressors to vaccination (n = 9; median OS, 56 months), compared with progressors (n = 18; median OS, 9.5 months). |
| 1124 | 24894091 | Our study shows that high numbers of intratumoral activated CD4(+) or CD8(+) T cells, before autologous tumor cell vaccination, are associated with favorable clinical outcome. |
| 1125 | 24904561 | Such studies have shown exhaustion of CD4(+) T cells and an unappreciated role for CD8(+) T cells in promoting sterile immunity against blood stage malaria. |
| 1126 | 24904561 | This is because PD-1 mediates up to a 95% reduction in numbers and functional capacity of parasite-specific CD8(+) T cells, thus masking their role in protection. |
| 1127 | 24943382 | However, the CD8(+) T-cell responses elicited by Ad5HVR48 vectors displayed a partially exhausted phenotype, as evidenced by the sustained expression of programmed death 1 (PD-1), decreased effector-to-central memory conversion, and reduced memory recall responses, similar to those elicited by Ad5 vectors and in contrast to those induced by Ad48 vectors. |
| 1128 | 24969320 | Monoclonal antibodies recognising melanoma-associated antigens such as CSPG4/MCSP and targeting elements of tumour-associated vasculature (VEGF) have constituted long-standing translational approaches aimed at reducing melanoma growth and metastasis. |
| 1129 | 24969320 | Recent insights into mechanisms of immune regulation and tumour-immune cell interactions have helped to identify checkpoint molecules on immune (CTLA4, PD-1) and tumour (PD-L1) cells as promising therapeutic targets. |
| 1130 | 24970795 | New immunotherapy drugs based on the release of the co-inhibitory receptors, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed-death 1 (PD-1) have currently emerged. |
| 1131 | 24990240 | Among the coadjuvants are (i) antagonists of A2AR, (ii) extracellular adenosine-degrading drugs, (iii) inhibitors of adenosine generation by CD39/CD73 ectoenzymes, and (iv) inhibitors of hypoxia-HIF-1α signaling. |
| 1132 | 24990240 | Combining these coadjuvants with CTLA-4 and/or PD-1 blockade is expected to have additive or even synergistic effects of targeting two different antitumor protective mechanisms. |
| 1133 | 24990240 | Yet to be tested is the potential capacity of coadjuvants to minimize the side effects of CTLA-4 and/or PD-1 blockade by decreasing the dose of blocking antibodies or by eliminating the need for dual blockade. |
| 1134 | 24990240 | Among the coadjuvants are (i) antagonists of A2AR, (ii) extracellular adenosine-degrading drugs, (iii) inhibitors of adenosine generation by CD39/CD73 ectoenzymes, and (iv) inhibitors of hypoxia-HIF-1α signaling. |
| 1135 | 24990240 | Combining these coadjuvants with CTLA-4 and/or PD-1 blockade is expected to have additive or even synergistic effects of targeting two different antitumor protective mechanisms. |
| 1136 | 24990240 | Yet to be tested is the potential capacity of coadjuvants to minimize the side effects of CTLA-4 and/or PD-1 blockade by decreasing the dose of blocking antibodies or by eliminating the need for dual blockade. |
| 1137 | 25066739 | We found that (1) the number of HIV-specific CD8 T cells was dramatically lower in GALT than in other tissues; (2) the programmed cell death protein-1 (PD-1) was expressed at high levels in HIV-specific CD8 T cells including memory T cells in GALT; and (3) high levels of HIV-specific CD8 T cell apoptosis were occurring in GALT. |
| 1138 | 25113973 | Rescue of exhausted CD8 T cells was dependent on cognate antigen, B7 costimulation, and conventional CD4 T cells. |
| 1139 | 25113973 | Interestingly, T reg cell ablation triggered up-regulation of the molecule programmed cell death ligand-1 (PD-L1), which upon binding PD-1 on T cells delivers inhibitory signals. |
| 1140 | 25113973 | These results suggest that T reg cells effectively maintain CD8 T cell exhaustion, but blockade of the PD-1 inhibitory pathway is critical for elimination of infected cells. |
| 1141 | 25113973 | Rescue of exhausted CD8 T cells was dependent on cognate antigen, B7 costimulation, and conventional CD4 T cells. |
| 1142 | 25113973 | Interestingly, T reg cell ablation triggered up-regulation of the molecule programmed cell death ligand-1 (PD-L1), which upon binding PD-1 on T cells delivers inhibitory signals. |
| 1143 | 25113973 | These results suggest that T reg cells effectively maintain CD8 T cell exhaustion, but blockade of the PD-1 inhibitory pathway is critical for elimination of infected cells. |
| 1144 | 25117757 | The relative contents of PD1(+) CD4(+) T-cells against total lymphocytes before and after the vaccination cycle correlated with overall survival (OS) with a high degree of statistical significance (P < 0.0001 and P = 0.0014). |
| 1145 | 25117757 | A decrease in PD-1(+) CD8(+) T-cells after one cycle of vaccination also correlated with longer OS (P = 0.032). |
| 1146 | 25117757 | The relative contents of PD1(+) CD4(+) T-cells against total lymphocytes before and after the vaccination cycle correlated with overall survival (OS) with a high degree of statistical significance (P < 0.0001 and P = 0.0014). |
| 1147 | 25117757 | A decrease in PD-1(+) CD8(+) T-cells after one cycle of vaccination also correlated with longer OS (P = 0.032). |
| 1148 | 25125656 | Also, these CD8(+) T cells functioned by releasing inflammatory IFNγ and TNFα in the vicinity of target cells as well as by initiating TRAIL-directed tumor cell apoptosis. |
| 1149 | 25125656 | Importantly, repeated DNA vaccinations, a major advantage over live-vectored vaccines with issues of preexisting immunity, achieve an active functional state, not only preventing the rise of exhausted PD-1(+) and Tim-3(+) CD8(+) T cells but also suppressing tumor-induced myeloid-derived suppressive cells and Treg cells, with the frequency of antigen-specific CD8(+) T cells inversely correlating with tumor mass. |
| 1150 | 25168392 | We used an orthotopic renal carcinoma model to evaluate the impact of injection routes on therapeutic efficacy of a Modified Vaccinia virus Ankara viral vector expressing the human mucin 1 tumor-associated xeno-antigen (MVA-MUC1). |
| 1151 | 25168392 | This appears to result in a faster generation of MUC1-specific CD8(+) T cells. |
| 1152 | 25168392 | Lymphocytes infiltrating tumor-bearing kidneys are characterized by an effector memory phenotype and express PD-1 and Tim3 immune checkpoint molecules. |
| 1153 | 25172499 | Circulating CXCR5+PD-1+ response predicts influenza vaccine antibody responses in young adults but not elderly adults. |
| 1154 | 25207460 | Next, the first immune-activating anticytotoxic lymphocyte antigen-4 (CTLA-4) antibody ipilimumab exhibiting 'immune checkpoint blockade' was approved by FDA and European Medical Agency (EMA) for the treatment of patients with metastatic melanoma. |
| 1155 | 25207460 | New generations of immune checkpoint blockading antibodies targeting programmed cell death 1 (PD-1) and its ligand (PD-L1) are now under intense investigation in metastatic melanoma (MM) and non-small-cell lung cancer (NSCLC), and impressive clinical results are anticipated. |
| 1156 | 25225461 | We show that the functional impairment of CD4 T cells, including the reduced capacity to proliferate and to produce IFN-γ and IL-2, was restricted to bacteria-specific and not virus-specific CD4 T cells. |
| 1157 | 25225461 | Of note, endotoxemia was associated with significantly higher expression of programmed death 1 (PD-1) on CD4 T cells. |
| 1158 | 25225461 | The blockade of the PD-1-PD-L1/2 axis in vitro restored CD4 T cell proliferation capacity, thus indicating that PD-1 signaling negatively regulates CD4 T cell functions. |
| 1159 | 25225461 | Finally, we showed that intravenous immunoglobulin G (IVIG) treatment significantly reduced endotoxemia and the percentage of PD-1(+) CD4 T cells, and restored bacteria-specific CD4 T cell cytokine production and proliferation. |
| 1160 | 25225461 | We show that the functional impairment of CD4 T cells, including the reduced capacity to proliferate and to produce IFN-γ and IL-2, was restricted to bacteria-specific and not virus-specific CD4 T cells. |
| 1161 | 25225461 | Of note, endotoxemia was associated with significantly higher expression of programmed death 1 (PD-1) on CD4 T cells. |
| 1162 | 25225461 | The blockade of the PD-1-PD-L1/2 axis in vitro restored CD4 T cell proliferation capacity, thus indicating that PD-1 signaling negatively regulates CD4 T cell functions. |
| 1163 | 25225461 | Finally, we showed that intravenous immunoglobulin G (IVIG) treatment significantly reduced endotoxemia and the percentage of PD-1(+) CD4 T cells, and restored bacteria-specific CD4 T cell cytokine production and proliferation. |
| 1164 | 25225461 | We show that the functional impairment of CD4 T cells, including the reduced capacity to proliferate and to produce IFN-γ and IL-2, was restricted to bacteria-specific and not virus-specific CD4 T cells. |
| 1165 | 25225461 | Of note, endotoxemia was associated with significantly higher expression of programmed death 1 (PD-1) on CD4 T cells. |
| 1166 | 25225461 | The blockade of the PD-1-PD-L1/2 axis in vitro restored CD4 T cell proliferation capacity, thus indicating that PD-1 signaling negatively regulates CD4 T cell functions. |
| 1167 | 25225461 | Finally, we showed that intravenous immunoglobulin G (IVIG) treatment significantly reduced endotoxemia and the percentage of PD-1(+) CD4 T cells, and restored bacteria-specific CD4 T cell cytokine production and proliferation. |
| 1168 | 25246494 | The inhibitory receptor programmed death-1 (PD-1) has been shown to regulate CD8 T cell function during chronic SIV infection; however, its role on CD4 T cells, specifically in the gut-associated lymphoid tissue, is less well understood. |
| 1169 | 25246494 | In this study, we show that a subset of CD4 T cells expresses high levels of PD-1 (PD-1(hi)) in the rectal mucosa, a preferential site of virus replication. |
| 1170 | 25246494 | The majority of these PD-1(hi) CD4 T cells expressed Bcl-6 and CXCR5, markers characteristic of T follicular helper cells in the lymph nodes. |
| 1171 | 25246494 | Following a pathogenic SIV infection, the frequency of PD-1(hi) cells (as a percentage of CD4 T cells) dramatically increased in the rectal mucosa; however, a significant fraction of them did not express CXCR5. |
| 1172 | 25246494 | Interestingly, vaccinated SIV controllers did not present with this aberrant PD-1(hi) CD4 T cell enrichment, and this lack of enrichment was associated with the presence of higher frequencies of SIV-specific granzyme B(+) CD8 T cells within the lymphoid tissue, suggesting a role for antiviral CD8 T cells in limiting aberrant expansion of PD-1(hi) CD4 T cells. |
| 1173 | 25246494 | These results highlight the importance of developing vaccines that enhance antiviral CD8 T cells at sites of preferential viral replication and support the need for developing therapeutic interventions that limit expansion of SIV(+)PD-1(hi) CD4 T cells at mucosal sites as a means to enhance viral control. |
| 1174 | 25246494 | The inhibitory receptor programmed death-1 (PD-1) has been shown to regulate CD8 T cell function during chronic SIV infection; however, its role on CD4 T cells, specifically in the gut-associated lymphoid tissue, is less well understood. |
| 1175 | 25246494 | In this study, we show that a subset of CD4 T cells expresses high levels of PD-1 (PD-1(hi)) in the rectal mucosa, a preferential site of virus replication. |
| 1176 | 25246494 | The majority of these PD-1(hi) CD4 T cells expressed Bcl-6 and CXCR5, markers characteristic of T follicular helper cells in the lymph nodes. |
| 1177 | 25246494 | Following a pathogenic SIV infection, the frequency of PD-1(hi) cells (as a percentage of CD4 T cells) dramatically increased in the rectal mucosa; however, a significant fraction of them did not express CXCR5. |
| 1178 | 25246494 | Interestingly, vaccinated SIV controllers did not present with this aberrant PD-1(hi) CD4 T cell enrichment, and this lack of enrichment was associated with the presence of higher frequencies of SIV-specific granzyme B(+) CD8 T cells within the lymphoid tissue, suggesting a role for antiviral CD8 T cells in limiting aberrant expansion of PD-1(hi) CD4 T cells. |
| 1179 | 25246494 | These results highlight the importance of developing vaccines that enhance antiviral CD8 T cells at sites of preferential viral replication and support the need for developing therapeutic interventions that limit expansion of SIV(+)PD-1(hi) CD4 T cells at mucosal sites as a means to enhance viral control. |
| 1180 | 25246494 | The inhibitory receptor programmed death-1 (PD-1) has been shown to regulate CD8 T cell function during chronic SIV infection; however, its role on CD4 T cells, specifically in the gut-associated lymphoid tissue, is less well understood. |
| 1181 | 25246494 | In this study, we show that a subset of CD4 T cells expresses high levels of PD-1 (PD-1(hi)) in the rectal mucosa, a preferential site of virus replication. |
| 1182 | 25246494 | The majority of these PD-1(hi) CD4 T cells expressed Bcl-6 and CXCR5, markers characteristic of T follicular helper cells in the lymph nodes. |
| 1183 | 25246494 | Following a pathogenic SIV infection, the frequency of PD-1(hi) cells (as a percentage of CD4 T cells) dramatically increased in the rectal mucosa; however, a significant fraction of them did not express CXCR5. |
| 1184 | 25246494 | Interestingly, vaccinated SIV controllers did not present with this aberrant PD-1(hi) CD4 T cell enrichment, and this lack of enrichment was associated with the presence of higher frequencies of SIV-specific granzyme B(+) CD8 T cells within the lymphoid tissue, suggesting a role for antiviral CD8 T cells in limiting aberrant expansion of PD-1(hi) CD4 T cells. |
| 1185 | 25246494 | These results highlight the importance of developing vaccines that enhance antiviral CD8 T cells at sites of preferential viral replication and support the need for developing therapeutic interventions that limit expansion of SIV(+)PD-1(hi) CD4 T cells at mucosal sites as a means to enhance viral control. |
| 1186 | 25246494 | The inhibitory receptor programmed death-1 (PD-1) has been shown to regulate CD8 T cell function during chronic SIV infection; however, its role on CD4 T cells, specifically in the gut-associated lymphoid tissue, is less well understood. |
| 1187 | 25246494 | In this study, we show that a subset of CD4 T cells expresses high levels of PD-1 (PD-1(hi)) in the rectal mucosa, a preferential site of virus replication. |
| 1188 | 25246494 | The majority of these PD-1(hi) CD4 T cells expressed Bcl-6 and CXCR5, markers characteristic of T follicular helper cells in the lymph nodes. |
| 1189 | 25246494 | Following a pathogenic SIV infection, the frequency of PD-1(hi) cells (as a percentage of CD4 T cells) dramatically increased in the rectal mucosa; however, a significant fraction of them did not express CXCR5. |
| 1190 | 25246494 | Interestingly, vaccinated SIV controllers did not present with this aberrant PD-1(hi) CD4 T cell enrichment, and this lack of enrichment was associated with the presence of higher frequencies of SIV-specific granzyme B(+) CD8 T cells within the lymphoid tissue, suggesting a role for antiviral CD8 T cells in limiting aberrant expansion of PD-1(hi) CD4 T cells. |
| 1191 | 25246494 | These results highlight the importance of developing vaccines that enhance antiviral CD8 T cells at sites of preferential viral replication and support the need for developing therapeutic interventions that limit expansion of SIV(+)PD-1(hi) CD4 T cells at mucosal sites as a means to enhance viral control. |
| 1192 | 25246494 | The inhibitory receptor programmed death-1 (PD-1) has been shown to regulate CD8 T cell function during chronic SIV infection; however, its role on CD4 T cells, specifically in the gut-associated lymphoid tissue, is less well understood. |
| 1193 | 25246494 | In this study, we show that a subset of CD4 T cells expresses high levels of PD-1 (PD-1(hi)) in the rectal mucosa, a preferential site of virus replication. |
| 1194 | 25246494 | The majority of these PD-1(hi) CD4 T cells expressed Bcl-6 and CXCR5, markers characteristic of T follicular helper cells in the lymph nodes. |
| 1195 | 25246494 | Following a pathogenic SIV infection, the frequency of PD-1(hi) cells (as a percentage of CD4 T cells) dramatically increased in the rectal mucosa; however, a significant fraction of them did not express CXCR5. |
| 1196 | 25246494 | Interestingly, vaccinated SIV controllers did not present with this aberrant PD-1(hi) CD4 T cell enrichment, and this lack of enrichment was associated with the presence of higher frequencies of SIV-specific granzyme B(+) CD8 T cells within the lymphoid tissue, suggesting a role for antiviral CD8 T cells in limiting aberrant expansion of PD-1(hi) CD4 T cells. |
| 1197 | 25246494 | These results highlight the importance of developing vaccines that enhance antiviral CD8 T cells at sites of preferential viral replication and support the need for developing therapeutic interventions that limit expansion of SIV(+)PD-1(hi) CD4 T cells at mucosal sites as a means to enhance viral control. |
| 1198 | 25246494 | The inhibitory receptor programmed death-1 (PD-1) has been shown to regulate CD8 T cell function during chronic SIV infection; however, its role on CD4 T cells, specifically in the gut-associated lymphoid tissue, is less well understood. |
| 1199 | 25246494 | In this study, we show that a subset of CD4 T cells expresses high levels of PD-1 (PD-1(hi)) in the rectal mucosa, a preferential site of virus replication. |
| 1200 | 25246494 | The majority of these PD-1(hi) CD4 T cells expressed Bcl-6 and CXCR5, markers characteristic of T follicular helper cells in the lymph nodes. |
| 1201 | 25246494 | Following a pathogenic SIV infection, the frequency of PD-1(hi) cells (as a percentage of CD4 T cells) dramatically increased in the rectal mucosa; however, a significant fraction of them did not express CXCR5. |
| 1202 | 25246494 | Interestingly, vaccinated SIV controllers did not present with this aberrant PD-1(hi) CD4 T cell enrichment, and this lack of enrichment was associated with the presence of higher frequencies of SIV-specific granzyme B(+) CD8 T cells within the lymphoid tissue, suggesting a role for antiviral CD8 T cells in limiting aberrant expansion of PD-1(hi) CD4 T cells. |
| 1203 | 25246494 | These results highlight the importance of developing vaccines that enhance antiviral CD8 T cells at sites of preferential viral replication and support the need for developing therapeutic interventions that limit expansion of SIV(+)PD-1(hi) CD4 T cells at mucosal sites as a means to enhance viral control. |
| 1204 | 25255144 | CD160-associated CD8 T-cell functional impairment is independent of PD-1 expression. |
| 1205 | 25255144 | In the present study, we have evaluated the impact of the expression of co-inhibitory molecules such as 2B4, PD-1 and CD160 on the functions of CD8 T-cells specific to influenza, EBV and CMV. |
| 1206 | 25255144 | We show that CD8 T-cell populations expressing CD160, but not PD-1, had reduced proliferation capacity and perforin expression, thus indicating that the functional impairment in CD160(+) CD8 T cells may be independent of PD-1 expression. |
| 1207 | 25255144 | The blockade of CD160/CD160-ligand interaction restored CD8 T-cell proliferation capacity, and the extent of restoration directly correlated with the ex vivo proportion of CD160(+) CD8 T cells suggesting that CD160 negatively regulates TCR-mediated signaling. |
| 1208 | 25255144 | Furthermore, CD160 expression was not up-regulated upon T-cell activation or proliferation as compared to PD-1. |
| 1209 | 25255144 | Taken together, these results provide evidence that CD160-associated CD8 T-cell functional impairment is independent of PD-1 expression. |
| 1210 | 25255144 | CD160-associated CD8 T-cell functional impairment is independent of PD-1 expression. |
| 1211 | 25255144 | In the present study, we have evaluated the impact of the expression of co-inhibitory molecules such as 2B4, PD-1 and CD160 on the functions of CD8 T-cells specific to influenza, EBV and CMV. |
| 1212 | 25255144 | We show that CD8 T-cell populations expressing CD160, but not PD-1, had reduced proliferation capacity and perforin expression, thus indicating that the functional impairment in CD160(+) CD8 T cells may be independent of PD-1 expression. |
| 1213 | 25255144 | The blockade of CD160/CD160-ligand interaction restored CD8 T-cell proliferation capacity, and the extent of restoration directly correlated with the ex vivo proportion of CD160(+) CD8 T cells suggesting that CD160 negatively regulates TCR-mediated signaling. |
| 1214 | 25255144 | Furthermore, CD160 expression was not up-regulated upon T-cell activation or proliferation as compared to PD-1. |
| 1215 | 25255144 | Taken together, these results provide evidence that CD160-associated CD8 T-cell functional impairment is independent of PD-1 expression. |
| 1216 | 25255144 | CD160-associated CD8 T-cell functional impairment is independent of PD-1 expression. |
| 1217 | 25255144 | In the present study, we have evaluated the impact of the expression of co-inhibitory molecules such as 2B4, PD-1 and CD160 on the functions of CD8 T-cells specific to influenza, EBV and CMV. |
| 1218 | 25255144 | We show that CD8 T-cell populations expressing CD160, but not PD-1, had reduced proliferation capacity and perforin expression, thus indicating that the functional impairment in CD160(+) CD8 T cells may be independent of PD-1 expression. |
| 1219 | 25255144 | The blockade of CD160/CD160-ligand interaction restored CD8 T-cell proliferation capacity, and the extent of restoration directly correlated with the ex vivo proportion of CD160(+) CD8 T cells suggesting that CD160 negatively regulates TCR-mediated signaling. |
| 1220 | 25255144 | Furthermore, CD160 expression was not up-regulated upon T-cell activation or proliferation as compared to PD-1. |
| 1221 | 25255144 | Taken together, these results provide evidence that CD160-associated CD8 T-cell functional impairment is independent of PD-1 expression. |
| 1222 | 25255144 | CD160-associated CD8 T-cell functional impairment is independent of PD-1 expression. |
| 1223 | 25255144 | In the present study, we have evaluated the impact of the expression of co-inhibitory molecules such as 2B4, PD-1 and CD160 on the functions of CD8 T-cells specific to influenza, EBV and CMV. |
| 1224 | 25255144 | We show that CD8 T-cell populations expressing CD160, but not PD-1, had reduced proliferation capacity and perforin expression, thus indicating that the functional impairment in CD160(+) CD8 T cells may be independent of PD-1 expression. |
| 1225 | 25255144 | The blockade of CD160/CD160-ligand interaction restored CD8 T-cell proliferation capacity, and the extent of restoration directly correlated with the ex vivo proportion of CD160(+) CD8 T cells suggesting that CD160 negatively regulates TCR-mediated signaling. |
| 1226 | 25255144 | Furthermore, CD160 expression was not up-regulated upon T-cell activation or proliferation as compared to PD-1. |
| 1227 | 25255144 | Taken together, these results provide evidence that CD160-associated CD8 T-cell functional impairment is independent of PD-1 expression. |
| 1228 | 25255144 | CD160-associated CD8 T-cell functional impairment is independent of PD-1 expression. |
| 1229 | 25255144 | In the present study, we have evaluated the impact of the expression of co-inhibitory molecules such as 2B4, PD-1 and CD160 on the functions of CD8 T-cells specific to influenza, EBV and CMV. |
| 1230 | 25255144 | We show that CD8 T-cell populations expressing CD160, but not PD-1, had reduced proliferation capacity and perforin expression, thus indicating that the functional impairment in CD160(+) CD8 T cells may be independent of PD-1 expression. |
| 1231 | 25255144 | The blockade of CD160/CD160-ligand interaction restored CD8 T-cell proliferation capacity, and the extent of restoration directly correlated with the ex vivo proportion of CD160(+) CD8 T cells suggesting that CD160 negatively regulates TCR-mediated signaling. |
| 1232 | 25255144 | Furthermore, CD160 expression was not up-regulated upon T-cell activation or proliferation as compared to PD-1. |
| 1233 | 25255144 | Taken together, these results provide evidence that CD160-associated CD8 T-cell functional impairment is independent of PD-1 expression. |
| 1234 | 25319657 | Depletion of tryptophan by IDO-positive DCs induces T-cell apoptosis and the conversion of naïve CD4+ T cells into regulatory T cells that further suppress antitumor immunity. |
| 1235 | 25319657 | Herein, we describe a protocol for in vitro synthesis of small interfering RNA against IDO and other immunosuppressive factors such as interleukin-10 and programmed cell death-1 ligands in order to reverse immune suppression mediated by DCs. |
| 1236 | 25320372 | In this article, we highlight these promising approaches, such as the combination of anti-CD20 antibodies with immunomodulatory drugs, with mAbs directed against other surface antigens such as CD22, with immunomodulatory antibodies such as PD-1, or with inhibitors of key steps in the B-cell receptor pathway signaling. |
| 1237 | 25323844 | Efforts to restore latent anti-tumor immunity have focused on antibody-based interventions targeting CTL antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) on T lymphocytes and its principal ligand (PD-L1) on tumor cells. |
| 1238 | 25323844 | Ipilimumab, an antibody targeting CTLA-4, appears to restore tumor immunity at the priming phase, whereas anti-PD-1/PD-L1 antibodies restore immune function in the tumor microenvironment. |
| 1239 | 25323844 | By contrast, antibodies targeting either PD-1 or PD-L1 have produced significant anti-tumor activity with considerably less toxicity. |
| 1240 | 25323844 | Efforts to restore latent anti-tumor immunity have focused on antibody-based interventions targeting CTL antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) on T lymphocytes and its principal ligand (PD-L1) on tumor cells. |
| 1241 | 25323844 | Ipilimumab, an antibody targeting CTLA-4, appears to restore tumor immunity at the priming phase, whereas anti-PD-1/PD-L1 antibodies restore immune function in the tumor microenvironment. |
| 1242 | 25323844 | By contrast, antibodies targeting either PD-1 or PD-L1 have produced significant anti-tumor activity with considerably less toxicity. |
| 1243 | 25339663 | Lung Ag-specific CD8(+) T cells (T(CD8)) are impaired during acute viral lower respiratory infection by the inhibitory receptor programmed death-1 (PD-1). |
| 1244 | 25339663 | A robust secondary effector lung TCD8 response was generated during reinfection, but these cells were more impaired and more highly expressed the inhibitory receptors PD-1, LAG-3, and 2B4 than primary T(CD8). |
| 1245 | 25339663 | In vivo therapeutic PD-1 blockade during HMPV reinfection restored lung T(CD8) effector functions (i.e., degranulation and cytokine production) and enhanced viral clearance. |
| 1246 | 25339663 | PD-1 also limited the protective efficacy of HMPV epitope-specific peptide vaccination and impaired lung T(CD8) during heterotypic influenza virus challenge infection. |
| 1247 | 25339663 | Lung Ag-specific CD8(+) T cells (T(CD8)) are impaired during acute viral lower respiratory infection by the inhibitory receptor programmed death-1 (PD-1). |
| 1248 | 25339663 | A robust secondary effector lung TCD8 response was generated during reinfection, but these cells were more impaired and more highly expressed the inhibitory receptors PD-1, LAG-3, and 2B4 than primary T(CD8). |
| 1249 | 25339663 | In vivo therapeutic PD-1 blockade during HMPV reinfection restored lung T(CD8) effector functions (i.e., degranulation and cytokine production) and enhanced viral clearance. |
| 1250 | 25339663 | PD-1 also limited the protective efficacy of HMPV epitope-specific peptide vaccination and impaired lung T(CD8) during heterotypic influenza virus challenge infection. |
| 1251 | 25339663 | Lung Ag-specific CD8(+) T cells (T(CD8)) are impaired during acute viral lower respiratory infection by the inhibitory receptor programmed death-1 (PD-1). |
| 1252 | 25339663 | A robust secondary effector lung TCD8 response was generated during reinfection, but these cells were more impaired and more highly expressed the inhibitory receptors PD-1, LAG-3, and 2B4 than primary T(CD8). |
| 1253 | 25339663 | In vivo therapeutic PD-1 blockade during HMPV reinfection restored lung T(CD8) effector functions (i.e., degranulation and cytokine production) and enhanced viral clearance. |
| 1254 | 25339663 | PD-1 also limited the protective efficacy of HMPV epitope-specific peptide vaccination and impaired lung T(CD8) during heterotypic influenza virus challenge infection. |
| 1255 | 25339663 | Lung Ag-specific CD8(+) T cells (T(CD8)) are impaired during acute viral lower respiratory infection by the inhibitory receptor programmed death-1 (PD-1). |
| 1256 | 25339663 | A robust secondary effector lung TCD8 response was generated during reinfection, but these cells were more impaired and more highly expressed the inhibitory receptors PD-1, LAG-3, and 2B4 than primary T(CD8). |
| 1257 | 25339663 | In vivo therapeutic PD-1 blockade during HMPV reinfection restored lung T(CD8) effector functions (i.e., degranulation and cytokine production) and enhanced viral clearance. |
| 1258 | 25339663 | PD-1 also limited the protective efficacy of HMPV epitope-specific peptide vaccination and impaired lung T(CD8) during heterotypic influenza virus challenge infection. |
| 1259 | 25340755 | CD4+ and CD8+ T cell activation are associated with HIV DNA in resting CD4+ T cells. |
| 1260 | 25340755 | We examined the association between multiple measurements of HIV and T cell activation (as defined by markers including CD38, HLA-DR, CCR5 and PD-1) in 30 antiretroviral-treated HIV-infected adults. |
| 1261 | 25340755 | We found a consistent association between the frequency of CD4+ and CD8+ T cells expressing HLA-DR and the frequency of resting CD4+ T cells containing HIV DNA. |
| 1262 | 25348621 | Expansion of dysfunctional Tim-3-expressing effector memory CD8+ T cells during simian immunodeficiency virus infection in rhesus macaques. |
| 1263 | 25348621 | The T cell Ig- and mucin domain-containing molecule-3 (Tim-3) negative immune checkpoint receptor demarcates functionally exhausted CD8(+) T cells arising from chronic stimulation in viral infections like HIV. |
| 1264 | 25348621 | Tim-3 blockade leads to improved antiviral CD8(+) T cell responses in vitro and, therefore, represents a novel intervention strategy to restore T cell function in vivo and protect from disease progression. |
| 1265 | 25348621 | We report that Tim-3(+)CD8(+) T cell frequencies are significantly increased in lymph nodes, but not in peripheral blood, in SIV-infected animals. |
| 1266 | 25348621 | Tim-3(+)PD-1(+)CD8(+) T cells are similarly increased during SIV infection and positively correlate with SIV plasma viremia. |
| 1267 | 25348621 | Tim-3 expression was found primarily on effector memory CD8(+) T cells in all tissues examined. |
| 1268 | 25348621 | Tim-3(+)CD8(+) T cells have lower Ki-67 content and minimal cytokine responses to SIV compared with Tim-3(-)CD8(+) T cells. |
| 1269 | 25348621 | During acute-phase SIV replication, Tim-3 expression peaked on SIV-specific CD8(+) T cells by 2 wk postinfection and then rapidly diminished, irrespective of mutational escape of cognate Ag, suggesting non-TCR-driven mechanisms for Tim-3 expression. |
| 1270 | 25348621 | Thus, rhesus Tim-3 in SIV infection partially mimics human Tim-3 in HIV infection and may serve as a novel model for targeted studies focused on rejuvenating HIV-specific CD8(+) T cell responses. |
| 1271 | 25354479 | Blocking the programmed death-1 (PD-1)/PD-L1 pathway is a rational strategy to overcome tumor escape and tolerance toward CTLs. |
| 1272 | 25354479 | The inhibitory receptor PD-1 was highly expressed in ex vivo GPC3-specific CTLs isolated from the PBMCs of vaccinated HCC patients. |
| 1273 | 25354479 | In addition, PD-1 blockade increased the number of GPC3-specific CTLs, which degranulate against liver cancer cell lines. |
| 1274 | 25354479 | This study demonstrated that PD-1/PD-L1 blockade augmented the antitumor effects of a peptide vaccine by increasing the immune response of vaccine-induced CTLs, and provided a foundation for the clinical development of a combination therapy using a GPC3 peptide vaccine and αPD-1 Ab. |
| 1275 | 25354479 | Blocking the programmed death-1 (PD-1)/PD-L1 pathway is a rational strategy to overcome tumor escape and tolerance toward CTLs. |
| 1276 | 25354479 | The inhibitory receptor PD-1 was highly expressed in ex vivo GPC3-specific CTLs isolated from the PBMCs of vaccinated HCC patients. |
| 1277 | 25354479 | In addition, PD-1 blockade increased the number of GPC3-specific CTLs, which degranulate against liver cancer cell lines. |
| 1278 | 25354479 | This study demonstrated that PD-1/PD-L1 blockade augmented the antitumor effects of a peptide vaccine by increasing the immune response of vaccine-induced CTLs, and provided a foundation for the clinical development of a combination therapy using a GPC3 peptide vaccine and αPD-1 Ab. |
| 1279 | 25354479 | Blocking the programmed death-1 (PD-1)/PD-L1 pathway is a rational strategy to overcome tumor escape and tolerance toward CTLs. |
| 1280 | 25354479 | The inhibitory receptor PD-1 was highly expressed in ex vivo GPC3-specific CTLs isolated from the PBMCs of vaccinated HCC patients. |
| 1281 | 25354479 | In addition, PD-1 blockade increased the number of GPC3-specific CTLs, which degranulate against liver cancer cell lines. |
| 1282 | 25354479 | This study demonstrated that PD-1/PD-L1 blockade augmented the antitumor effects of a peptide vaccine by increasing the immune response of vaccine-induced CTLs, and provided a foundation for the clinical development of a combination therapy using a GPC3 peptide vaccine and αPD-1 Ab. |
| 1283 | 25354479 | Blocking the programmed death-1 (PD-1)/PD-L1 pathway is a rational strategy to overcome tumor escape and tolerance toward CTLs. |
| 1284 | 25354479 | The inhibitory receptor PD-1 was highly expressed in ex vivo GPC3-specific CTLs isolated from the PBMCs of vaccinated HCC patients. |
| 1285 | 25354479 | In addition, PD-1 blockade increased the number of GPC3-specific CTLs, which degranulate against liver cancer cell lines. |
| 1286 | 25354479 | This study demonstrated that PD-1/PD-L1 blockade augmented the antitumor effects of a peptide vaccine by increasing the immune response of vaccine-induced CTLs, and provided a foundation for the clinical development of a combination therapy using a GPC3 peptide vaccine and αPD-1 Ab. |
| 1287 | 25382117 | Although the disappointing data deriving from the employment of vaccines in non-small cell lung cancer (NSCLC), more promising results have been obtained in the early phase trials with immune checkpoint inhibitors, such as cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), programmed cell death protein-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors. |
| 1288 | 25386340 | The combination of vaccines with new immuno-stimulating agents which target "immunosuppressive checkpoints" (anti-CTLA-4, PD-1, etc.) is likely to improve and maintain immune response induced by vaccination. |
| 1289 | 25387892 | Combination of 4-1BB agonist and PD-1 antagonist promotes antitumor effector/memory CD8 T cells in a poorly immunogenic tumor model. |
| 1290 | 25387892 | The activity of the anti-4-1BB/anti-PD-1 combination was dependent on IFNγ and CD8(+) T cells. |
| 1291 | 25387892 | Both 4-1BB and PD-1 proteins were elevated on the surface of CD8(+) T cells by anti-4-1BB/anti-PD-1 cotreatment. |
| 1292 | 25387892 | In the tumor microenvironment, an effective antitumor immune response was induced as indicated by the increased CD8(+)/Treg ratio and the enrichment of genes such as Cd3e, Cd8a, Ifng, and Eomes. |
| 1293 | 25387892 | Combination of 4-1BB agonist and PD-1 antagonist promotes antitumor effector/memory CD8 T cells in a poorly immunogenic tumor model. |
| 1294 | 25387892 | The activity of the anti-4-1BB/anti-PD-1 combination was dependent on IFNγ and CD8(+) T cells. |
| 1295 | 25387892 | Both 4-1BB and PD-1 proteins were elevated on the surface of CD8(+) T cells by anti-4-1BB/anti-PD-1 cotreatment. |
| 1296 | 25387892 | In the tumor microenvironment, an effective antitumor immune response was induced as indicated by the increased CD8(+)/Treg ratio and the enrichment of genes such as Cd3e, Cd8a, Ifng, and Eomes. |
| 1297 | 25415283 | PD-1/PD-L1 blockade together with vaccine therapy facilitates effector T-cell infiltration into pancreatic tumors. |
| 1298 | 25415283 | However, single-agent checkpoint inhibitors including agents that alter immune suppressive signals in other human cancers such as cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed death 1 (PD-1), and its ligand PD-L1, have failed to demonstrate objective responses when given as single agents to PDA patients. |
| 1299 | 25415283 | In this study, we evaluated blockade of the PD-1/PD-L1 pathway. |
| 1300 | 25415283 | We found that PD-L1 is weakly expressed at a low frequency in untreated human and murine PDAs but treatment with a granulocyte macrophage colony-stimulating factor secreting PDA vaccine (GVAX) significantly upregulates PD-L1 membranous expression after treatment of tumor-bearing mice. |
| 1301 | 25415283 | Furthermore, PD-1 blockade increased effector CD8 T lymphocytes and tumor-specific interferon-γ production of CD8 T cells in the tumor microenvironment. |
| 1302 | 25415283 | Immunosuppressive pathways, including regulatory T cells and CTLA-4 expression on T cells were overcome by the addition of vaccine and low-dose cyclophosphamide to PD-1 blockade. |
| 1303 | 25415283 | Collectively, our study supports combining PD-1 or PD-L1 antibody therapy with a T cell inducing agent for PDA treatment. |
| 1304 | 25415283 | PD-1/PD-L1 blockade together with vaccine therapy facilitates effector T-cell infiltration into pancreatic tumors. |
| 1305 | 25415283 | However, single-agent checkpoint inhibitors including agents that alter immune suppressive signals in other human cancers such as cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed death 1 (PD-1), and its ligand PD-L1, have failed to demonstrate objective responses when given as single agents to PDA patients. |
| 1306 | 25415283 | In this study, we evaluated blockade of the PD-1/PD-L1 pathway. |
| 1307 | 25415283 | We found that PD-L1 is weakly expressed at a low frequency in untreated human and murine PDAs but treatment with a granulocyte macrophage colony-stimulating factor secreting PDA vaccine (GVAX) significantly upregulates PD-L1 membranous expression after treatment of tumor-bearing mice. |
| 1308 | 25415283 | Furthermore, PD-1 blockade increased effector CD8 T lymphocytes and tumor-specific interferon-γ production of CD8 T cells in the tumor microenvironment. |
| 1309 | 25415283 | Immunosuppressive pathways, including regulatory T cells and CTLA-4 expression on T cells were overcome by the addition of vaccine and low-dose cyclophosphamide to PD-1 blockade. |
| 1310 | 25415283 | Collectively, our study supports combining PD-1 or PD-L1 antibody therapy with a T cell inducing agent for PDA treatment. |
| 1311 | 25415283 | PD-1/PD-L1 blockade together with vaccine therapy facilitates effector T-cell infiltration into pancreatic tumors. |
| 1312 | 25415283 | However, single-agent checkpoint inhibitors including agents that alter immune suppressive signals in other human cancers such as cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed death 1 (PD-1), and its ligand PD-L1, have failed to demonstrate objective responses when given as single agents to PDA patients. |
| 1313 | 25415283 | In this study, we evaluated blockade of the PD-1/PD-L1 pathway. |
| 1314 | 25415283 | We found that PD-L1 is weakly expressed at a low frequency in untreated human and murine PDAs but treatment with a granulocyte macrophage colony-stimulating factor secreting PDA vaccine (GVAX) significantly upregulates PD-L1 membranous expression after treatment of tumor-bearing mice. |
| 1315 | 25415283 | Furthermore, PD-1 blockade increased effector CD8 T lymphocytes and tumor-specific interferon-γ production of CD8 T cells in the tumor microenvironment. |
| 1316 | 25415283 | Immunosuppressive pathways, including regulatory T cells and CTLA-4 expression on T cells were overcome by the addition of vaccine and low-dose cyclophosphamide to PD-1 blockade. |
| 1317 | 25415283 | Collectively, our study supports combining PD-1 or PD-L1 antibody therapy with a T cell inducing agent for PDA treatment. |
| 1318 | 25415283 | PD-1/PD-L1 blockade together with vaccine therapy facilitates effector T-cell infiltration into pancreatic tumors. |
| 1319 | 25415283 | However, single-agent checkpoint inhibitors including agents that alter immune suppressive signals in other human cancers such as cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed death 1 (PD-1), and its ligand PD-L1, have failed to demonstrate objective responses when given as single agents to PDA patients. |
| 1320 | 25415283 | In this study, we evaluated blockade of the PD-1/PD-L1 pathway. |
| 1321 | 25415283 | We found that PD-L1 is weakly expressed at a low frequency in untreated human and murine PDAs but treatment with a granulocyte macrophage colony-stimulating factor secreting PDA vaccine (GVAX) significantly upregulates PD-L1 membranous expression after treatment of tumor-bearing mice. |
| 1322 | 25415283 | Furthermore, PD-1 blockade increased effector CD8 T lymphocytes and tumor-specific interferon-γ production of CD8 T cells in the tumor microenvironment. |
| 1323 | 25415283 | Immunosuppressive pathways, including regulatory T cells and CTLA-4 expression on T cells were overcome by the addition of vaccine and low-dose cyclophosphamide to PD-1 blockade. |
| 1324 | 25415283 | Collectively, our study supports combining PD-1 or PD-L1 antibody therapy with a T cell inducing agent for PDA treatment. |
| 1325 | 25415283 | PD-1/PD-L1 blockade together with vaccine therapy facilitates effector T-cell infiltration into pancreatic tumors. |
| 1326 | 25415283 | However, single-agent checkpoint inhibitors including agents that alter immune suppressive signals in other human cancers such as cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed death 1 (PD-1), and its ligand PD-L1, have failed to demonstrate objective responses when given as single agents to PDA patients. |
| 1327 | 25415283 | In this study, we evaluated blockade of the PD-1/PD-L1 pathway. |
| 1328 | 25415283 | We found that PD-L1 is weakly expressed at a low frequency in untreated human and murine PDAs but treatment with a granulocyte macrophage colony-stimulating factor secreting PDA vaccine (GVAX) significantly upregulates PD-L1 membranous expression after treatment of tumor-bearing mice. |
| 1329 | 25415283 | Furthermore, PD-1 blockade increased effector CD8 T lymphocytes and tumor-specific interferon-γ production of CD8 T cells in the tumor microenvironment. |
| 1330 | 25415283 | Immunosuppressive pathways, including regulatory T cells and CTLA-4 expression on T cells were overcome by the addition of vaccine and low-dose cyclophosphamide to PD-1 blockade. |
| 1331 | 25415283 | Collectively, our study supports combining PD-1 or PD-L1 antibody therapy with a T cell inducing agent for PDA treatment. |
| 1332 | 25415283 | PD-1/PD-L1 blockade together with vaccine therapy facilitates effector T-cell infiltration into pancreatic tumors. |
| 1333 | 25415283 | However, single-agent checkpoint inhibitors including agents that alter immune suppressive signals in other human cancers such as cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed death 1 (PD-1), and its ligand PD-L1, have failed to demonstrate objective responses when given as single agents to PDA patients. |
| 1334 | 25415283 | In this study, we evaluated blockade of the PD-1/PD-L1 pathway. |
| 1335 | 25415283 | We found that PD-L1 is weakly expressed at a low frequency in untreated human and murine PDAs but treatment with a granulocyte macrophage colony-stimulating factor secreting PDA vaccine (GVAX) significantly upregulates PD-L1 membranous expression after treatment of tumor-bearing mice. |
| 1336 | 25415283 | Furthermore, PD-1 blockade increased effector CD8 T lymphocytes and tumor-specific interferon-γ production of CD8 T cells in the tumor microenvironment. |
| 1337 | 25415283 | Immunosuppressive pathways, including regulatory T cells and CTLA-4 expression on T cells were overcome by the addition of vaccine and low-dose cyclophosphamide to PD-1 blockade. |
| 1338 | 25415283 | Collectively, our study supports combining PD-1 or PD-L1 antibody therapy with a T cell inducing agent for PDA treatment. |
| 1339 | 25428507 | In many individuals, immunosuppression is mediated by cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and programmed death-1 (PD-1), two immunomodulatory receptors expressed on T cells. |
| 1340 | 25428507 | Monoclonal-antibody-based therapies targeting CTLA-4 and/or PD-1 (checkpoint blockade) have yielded significant clinical benefits-including durable responses--to patients with different malignancies. |
| 1341 | 25428507 | In many individuals, immunosuppression is mediated by cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and programmed death-1 (PD-1), two immunomodulatory receptors expressed on T cells. |
| 1342 | 25428507 | Monoclonal-antibody-based therapies targeting CTLA-4 and/or PD-1 (checkpoint blockade) have yielded significant clinical benefits-including durable responses--to patients with different malignancies. |
| 1343 | 25483636 | After 48 hours, CD4+ and CD8+ T cells were harvested from both groups and stained for PD-1/CD25/ FOXP3. |
| 1344 | 25483636 | Similarly, in terms of PD-1 expression and Treg cells (CD4+/CD25high(+)/FOXP3+), only the HD group showed higher levels in CD4 lymphocytes. |
| 1345 | 25483636 | In terms of cytokines, the HD group showed higher levels of Th1 (IL-2/TNF-α/IFN-γ) and regulatory (IL-10) profiles, with monocytes, but not Tr1 cells, acting as the main source of IL-10. |
| 1346 | 25483636 | After 48 hours, CD4+ and CD8+ T cells were harvested from both groups and stained for PD-1/CD25/ FOXP3. |
| 1347 | 25483636 | Similarly, in terms of PD-1 expression and Treg cells (CD4+/CD25high(+)/FOXP3+), only the HD group showed higher levels in CD4 lymphocytes. |
| 1348 | 25483636 | In terms of cytokines, the HD group showed higher levels of Th1 (IL-2/TNF-α/IFN-γ) and regulatory (IL-10) profiles, with monocytes, but not Tr1 cells, acting as the main source of IL-10. |
| 1349 | 25540326 | RAD001 also reduced the percentage of CD4 and CD8 T lymphocytes expressing the programmed death-1 (PD-1) receptor, which inhibits T cell signaling and is more highly expressed with age. |
| 1350 | 25583297 | Several of these agents, such as antibodies targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed death receptor 1 (PD-1) have already demonstrated significant promise in clinical trials. |
| 1351 | 25595788 | Vaccines against mucosally invasive, intracellular pathogens must induce a myriad of immune responses to provide optimal mucosal and systemic protection, including CD4(+) T cells, CD8(+) T cells, and Ab-producing B cells. |
| 1352 | 25595788 | In general, CD4(+) T cells are known to provide important helper functions for both CD8(+) T cell and B cell responses. |
| 1353 | 25595788 | However, the relative importance of CD4(+) T cells, CD8(+) T cells, and B cells for mucosal protection is less clearly defined. |
| 1354 | 25595788 | Mechanistically, T. cruzi-specific CD8(+) T cells generated in the absence of B cells expressed increased PD-1 and Lag-3 and became functionally exhausted after high-level T. cruzi systemic challenge. |
| 1355 | 25624476 | In addition, it increased the number of CD8(+) tumor-infiltrating lymphocytes (TILs) and protected them from apoptosis and exhaustion characterized by decreased production of IL-2, TNFα, and IFNγ. |
| 1356 | 25624476 | CD8(+) TILs capable of producing multiple cytokines were mainly PD-1(-)Tim-3(+), an effector memory subset responsible for tumor rejection. |
| 1357 | 25624476 | Combined use of metformin and cancer vaccine improved CD8(+) TIL multifunctionality. |
| 1358 | 25624476 | The adoptive transfer of antigen-specific CD8(+) T cells treated with metformin concentrations as low as 10 μM showed efficient migration into tumors while maintaining multifunctionality in a manner sensitive to the AMP-activated protein kinase (AMPK) inhibitor compound C. |
| 1359 | 25625924 | PD-1 and PD-L1 antibodies for melanoma. |
| 1360 | 25625924 | Recognition of the immunogenic nature of melanoma has resulted in the development of various immunotherapeutic approaches, especially with regards to the programmed cell death 1 (PD-1) receptor and its ligand (PD-L1). |
| 1361 | 25625924 | Here, we will review the immune basis for the disease and discuss approved immunotherapeutic options for advanced melanoma, as well as the current state of development of PD-1 and PD-L1 antibodies and their importance in shaping the future of melanoma treatment. |
| 1362 | 25625924 | PD-1 and PD-L1 antibodies for melanoma. |
| 1363 | 25625924 | Recognition of the immunogenic nature of melanoma has resulted in the development of various immunotherapeutic approaches, especially with regards to the programmed cell death 1 (PD-1) receptor and its ligand (PD-L1). |
| 1364 | 25625924 | Here, we will review the immune basis for the disease and discuss approved immunotherapeutic options for advanced melanoma, as well as the current state of development of PD-1 and PD-L1 antibodies and their importance in shaping the future of melanoma treatment. |
| 1365 | 25625924 | PD-1 and PD-L1 antibodies for melanoma. |
| 1366 | 25625924 | Recognition of the immunogenic nature of melanoma has resulted in the development of various immunotherapeutic approaches, especially with regards to the programmed cell death 1 (PD-1) receptor and its ligand (PD-L1). |
| 1367 | 25625924 | Here, we will review the immune basis for the disease and discuss approved immunotherapeutic options for advanced melanoma, as well as the current state of development of PD-1 and PD-L1 antibodies and their importance in shaping the future of melanoma treatment. |
| 1368 | 25625932 | This review compares the optimal use of vaccines vs. other forms of immunotherapy, which includes cytokines, such as IL-2, monoclonal antibodies, such as the 'checkpoint inhibitors', against CTLA-4 and PD-1. |
| 1369 | 25668078 | Early clinical trials have demonstrated meaningful response rates, sustained clinical benefits with encouraging survival rates and good tolerability of next-generation checkpoint inhibitors, including programmed death-1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors, across multiple cancer types. |
| 1370 | 25692916 | We recently reported the identification of Δ42PD1, a novel alternatively spliced isoform of human PD1 that induces the production of pro-inflammatory cytokines from human peripheral blood mononuclear cells and enhances HIV-specific CD8(+) T cell immunity in mice when engineered in a fusion DNA vaccine. |
| 1371 | 25692916 | Since the level of Δ42PD1 expression on CD14(+) monocytes was negatively correlated with the CD4 count of untreated patients in a cross-sectional study, Δ42PD1 may play a role in HIV-1 pathogenesis. |
| 1372 | 25697584 | Immune checkpoint blockade with anti-cytotoxic T lymphocyte antigen-4 (CTLA) and anti-programmed cell death 1 (PD-1) have demonstrated encouraging results in clinical trials with other solid tumors, and recent data suggest that this type of therapy may be particularly useful for tumors with high mutational burdens. |
| 1373 | 25724840 | siRNA silencing of PD-1 ligands on dendritic cell vaccines boosts the expansion of minor histocompatibility antigen-specific CD8(+) T cells in NOD/SCID/IL2Rg(null) mice. |
| 1374 | 25724840 | Co-culturing CD8(+) T cells with MiHA-loaded DCs resulted in priming and expansion of functional MiHA-specific CD8(+) T cells from the naive repertoire, which was augmented upon silencing of PD-L1 and PD-L2. |
| 1375 | 25733707 | Blocking inhibitory pathways such as the CTL antigen 4 (CTLA-4) and programmed cell death 1 (PD-1) checkpoint pathways with mAbs has generated antitumor immune responses that are transforming cancer therapeutics. |
| 1376 | 25733707 | PD-1 and programmed cell death ligand 1 (PD-L1) antibodies have shown durable responses in NSCLC, with a favorable safety profile and manageable side effects. |
| 1377 | 25733707 | Blocking inhibitory pathways such as the CTL antigen 4 (CTLA-4) and programmed cell death 1 (PD-1) checkpoint pathways with mAbs has generated antitumor immune responses that are transforming cancer therapeutics. |
| 1378 | 25733707 | PD-1 and programmed cell death ligand 1 (PD-L1) antibodies have shown durable responses in NSCLC, with a favorable safety profile and manageable side effects. |
| 1379 | 25751647 | A diverse array of immunotherapeutic strategies have entered clinical trials in myeloma, including PD-1/PD-L1 inhibitors, DC/myeloma cell fusion vaccines and adoptive chimeric Ag receptor T-cell therapy, and further investigation of combinations of immunologic and pharmaceutical agents are expected in the near future. |
| 1380 | 25792524 | The vaccines were aimed at activating type I CD4(+)T cells and consisted of tumor cells transfected with genes encoding syngeneic MHC class II and CD80 costimulatory molecules, and lacking the MHC II-associated invariant chain. |
| 1381 | 25792524 | During the course of the vaccine studies, we observed that CD80 not only costimulated naïve T cells, but also bound to PD-L1 and prevented tumor cell-expressed PD-L1 from binding to its receptor PD-1 on activated T cells. |
| 1382 | 25792524 | A soluble form of CD80 (CD80-Fc) had the same effect and sustained IFNγ production by both human and murine PD-1(+) activated T cells in the presence of PD-L1(+) human or mouse tumor cells, respectively. |
| 1383 | 25792524 | In vitro studies with human tumor cells indicated that CD80-Fc was more effective than antibodies to either PD-1 or PD-L1 in sustaining T cell production of IFNγ. |
| 1384 | 25792524 | Studies with human T cells blocked for CD28 and with T cells from CD28 knockout mice demonstrated that CD80-Fc simultaneously inhibited PD-L1/PD-1-mediated immune suppression and delivered costimulatory signals to activated T cells, thereby amplifying T cell activation. |
| 1385 | 25792524 | The vaccines were aimed at activating type I CD4(+)T cells and consisted of tumor cells transfected with genes encoding syngeneic MHC class II and CD80 costimulatory molecules, and lacking the MHC II-associated invariant chain. |
| 1386 | 25792524 | During the course of the vaccine studies, we observed that CD80 not only costimulated naïve T cells, but also bound to PD-L1 and prevented tumor cell-expressed PD-L1 from binding to its receptor PD-1 on activated T cells. |
| 1387 | 25792524 | A soluble form of CD80 (CD80-Fc) had the same effect and sustained IFNγ production by both human and murine PD-1(+) activated T cells in the presence of PD-L1(+) human or mouse tumor cells, respectively. |
| 1388 | 25792524 | In vitro studies with human tumor cells indicated that CD80-Fc was more effective than antibodies to either PD-1 or PD-L1 in sustaining T cell production of IFNγ. |
| 1389 | 25792524 | Studies with human T cells blocked for CD28 and with T cells from CD28 knockout mice demonstrated that CD80-Fc simultaneously inhibited PD-L1/PD-1-mediated immune suppression and delivered costimulatory signals to activated T cells, thereby amplifying T cell activation. |
| 1390 | 25792524 | The vaccines were aimed at activating type I CD4(+)T cells and consisted of tumor cells transfected with genes encoding syngeneic MHC class II and CD80 costimulatory molecules, and lacking the MHC II-associated invariant chain. |
| 1391 | 25792524 | During the course of the vaccine studies, we observed that CD80 not only costimulated naïve T cells, but also bound to PD-L1 and prevented tumor cell-expressed PD-L1 from binding to its receptor PD-1 on activated T cells. |
| 1392 | 25792524 | A soluble form of CD80 (CD80-Fc) had the same effect and sustained IFNγ production by both human and murine PD-1(+) activated T cells in the presence of PD-L1(+) human or mouse tumor cells, respectively. |
| 1393 | 25792524 | In vitro studies with human tumor cells indicated that CD80-Fc was more effective than antibodies to either PD-1 or PD-L1 in sustaining T cell production of IFNγ. |
| 1394 | 25792524 | Studies with human T cells blocked for CD28 and with T cells from CD28 knockout mice demonstrated that CD80-Fc simultaneously inhibited PD-L1/PD-1-mediated immune suppression and delivered costimulatory signals to activated T cells, thereby amplifying T cell activation. |
| 1395 | 25806276 | Immune checkpoint therapies include the monoclonal antibody blockade of the cytotoxic T-lymphocyte antigen-4 (CTLA-4) with ipilimumab, as well as antibody blockade of the programmed cell death-1 (PD-1) receptor and the PD-1 ligand. |
| 1396 | 25806276 | In lung cancer, these include the melanoma-associated antigen-A3 (MAGE-A3), membrane-associated glycoprotein (MUC-1), and the epidermal growth factor receptor (EGFR). |
| 1397 | 25806281 | In particular, the checkpoint inhibitors targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the programmed death-1 (PD-1) pathway have shown durable clinical responses with manageable toxicity. |
| 1398 | 25810391 | Despite its importance, the mechanisms that regulate PD-1 in cell types other than CD8 T cells are poorly defined. |
| 1399 | 25810391 | In this study, the molecular mechanisms for inducing PD-1 expression in CD4 T cells, macrophages, and B cells were explored. |
| 1400 | 25810391 | In CD4 T cells, PD-1 induction following TCR stimulation required NFAT, as the calcineurin/NFAT pathway inhibitor cyclosporin A was able to block PD-1 induction in a manner similar to that seen in CD8 T cells. |
| 1401 | 25810391 | PD-1 induction was associated with histone modifications characteristic of accessible chromatin; however, in contrast to CD8 T cells, conserved region B in macrophages did not lose CpG methylation upon stimulation and PD-1 expression. |
| 1402 | 25810391 | Despite its importance, the mechanisms that regulate PD-1 in cell types other than CD8 T cells are poorly defined. |
| 1403 | 25810391 | In this study, the molecular mechanisms for inducing PD-1 expression in CD4 T cells, macrophages, and B cells were explored. |
| 1404 | 25810391 | In CD4 T cells, PD-1 induction following TCR stimulation required NFAT, as the calcineurin/NFAT pathway inhibitor cyclosporin A was able to block PD-1 induction in a manner similar to that seen in CD8 T cells. |
| 1405 | 25810391 | PD-1 induction was associated with histone modifications characteristic of accessible chromatin; however, in contrast to CD8 T cells, conserved region B in macrophages did not lose CpG methylation upon stimulation and PD-1 expression. |
| 1406 | 25810391 | Despite its importance, the mechanisms that regulate PD-1 in cell types other than CD8 T cells are poorly defined. |
| 1407 | 25810391 | In this study, the molecular mechanisms for inducing PD-1 expression in CD4 T cells, macrophages, and B cells were explored. |
| 1408 | 25810391 | In CD4 T cells, PD-1 induction following TCR stimulation required NFAT, as the calcineurin/NFAT pathway inhibitor cyclosporin A was able to block PD-1 induction in a manner similar to that seen in CD8 T cells. |
| 1409 | 25810391 | PD-1 induction was associated with histone modifications characteristic of accessible chromatin; however, in contrast to CD8 T cells, conserved region B in macrophages did not lose CpG methylation upon stimulation and PD-1 expression. |
| 1410 | 25810391 | Despite its importance, the mechanisms that regulate PD-1 in cell types other than CD8 T cells are poorly defined. |
| 1411 | 25810391 | In this study, the molecular mechanisms for inducing PD-1 expression in CD4 T cells, macrophages, and B cells were explored. |
| 1412 | 25810391 | In CD4 T cells, PD-1 induction following TCR stimulation required NFAT, as the calcineurin/NFAT pathway inhibitor cyclosporin A was able to block PD-1 induction in a manner similar to that seen in CD8 T cells. |
| 1413 | 25810391 | PD-1 induction was associated with histone modifications characteristic of accessible chromatin; however, in contrast to CD8 T cells, conserved region B in macrophages did not lose CpG methylation upon stimulation and PD-1 expression. |
| 1414 | 25824455 | Enhanced signalling of the Programmed cell death-1 (PDCD1, PD-1)/cytotoxic T-lymphocyte-associated protein 4 (CTLA4) 'immune checkpoint' pathway has emerged recently as a critical mechanism by which tumours can escape the natural anti-tumour immune response. |
| 1415 | 25824455 | As such, novel therapies have been developed to help enhance this natural immunity by switching off the PDCD1/CTLA4 immune checkpoint pathway. |
| 1416 | 25824455 | Enhanced signalling of the Programmed cell death-1 (PDCD1, PD-1)/cytotoxic T-lymphocyte-associated protein 4 (CTLA4) 'immune checkpoint' pathway has emerged recently as a critical mechanism by which tumours can escape the natural anti-tumour immune response. |
| 1417 | 25824455 | As such, novel therapies have been developed to help enhance this natural immunity by switching off the PDCD1/CTLA4 immune checkpoint pathway. |
| 1418 | 25825451 | Programmed cell death 1 and Helios distinguish TCR-αβ+ double-negative (CD4-CD8-) T cells that derive from self-reactive CD8 T cells. |
| 1419 | 25825451 | We also show that DN T cells derived from self-reactive CD8 cells express the inhibitory molecules PD-1 and Helios. |
| 1420 | 25825451 | Collectively, our data suggest that a subset of DN T cells, identified by the expression of PD-1 and Helios, represent self-reactive cells. |
| 1421 | 25825451 | Programmed cell death 1 and Helios distinguish TCR-αβ+ double-negative (CD4-CD8-) T cells that derive from self-reactive CD8 T cells. |
| 1422 | 25825451 | We also show that DN T cells derived from self-reactive CD8 cells express the inhibitory molecules PD-1 and Helios. |
| 1423 | 25825451 | Collectively, our data suggest that a subset of DN T cells, identified by the expression of PD-1 and Helios, represent self-reactive cells. |
| 1424 | 25825451 | Programmed cell death 1 and Helios distinguish TCR-αβ+ double-negative (CD4-CD8-) T cells that derive from self-reactive CD8 T cells. |
| 1425 | 25825451 | We also show that DN T cells derived from self-reactive CD8 cells express the inhibitory molecules PD-1 and Helios. |
| 1426 | 25825451 | Collectively, our data suggest that a subset of DN T cells, identified by the expression of PD-1 and Helios, represent self-reactive cells. |
| 1427 | 25870800 | It is accomplished by M2 macrophage polarization, the activity of myeloid derived suppressor cells (MDSCs) and a significantly elevated concentration of cytokines: transforming growth factor beta (TGFβ) and IL-10 in the tumor microenvironment. |
| 1428 | 25870800 | Very active suppression of immune protection is the predominant role of the programmed death 1 (PD-1)-PD-L1 pathway. |
| 1429 | 25870800 | Cytotoxic T lymphocyte antigen-4 (CTLA-4) is the molecule capable of inhibiting the activation signal. |
| 1430 | 25870800 | The second way in lung cancer immunotherapy is production of anti-cancer vaccines using recognized cancer antigens: MAGE-A3, membrane associated glycoprotein (MUC-1), and EGF. |
| 1431 | 25873269 | ALDH, CD44, CD133, and HER2 have served as markers to isolate CSCs from a number of tumor types in animal models and human tumors. |
| 1432 | 25873269 | Targeting the tumor microenvironment, such as interrupting the immune cell, for example, myeloid-derived suppressor cells, and cytokines, for example, IL-6 and IL-8, as well as the immune checkpoint (PD1/PDL1, etc.) may provide additional novel strategies to enhance the immunological targeting of CSCs. |
| 1433 | 25878105 | Therapeutic immunization with a mixture of herpes simplex virus 1 glycoprotein D-derived “asymptomatic” human CD8+ T-cell epitopes decreases spontaneous ocular shedding in latently infected HLA transgenic rabbits: association with low frequency of local PD-1+ TIM-3+ CD8+ exhausted T cells. |
| 1434 | 25883386 | Elevated Expression of CD160 and 2B4 Defines a Cytolytic HIV-Specific CD8+ T-Cell Population in Elite Controllers. |
| 1435 | 25883386 | Here we assessed coexpression of PD-1, Lag-3, CD160, and 2B4 as a measure of T-cell exhaustion in a cohort of elite controllers and in chronic progressors. |
| 1436 | 25883386 | We found that elite controllers have a high proportion of potentially exhausted (PD1(+)CD160(+)2B4(+)) HIV-specific CD8(+) T cells that is comparable to the proportion in chronic progressors. |
| 1437 | 25883386 | However, elite controllers also harbor a population of HIV-specific CD160(+)2B4(+) CD8(+) T cells that correlates with cytolytic capacity, as measured by perforin expression, a population not commonly present in chronic progressors. |
| 1438 | 25883386 | We therefore propose that coexpression of CD160 and 2B4 delineates a population of cytolytic CD8(+) T cells important for the control of HIV. |
| 1439 | 25883386 | Elevated Expression of CD160 and 2B4 Defines a Cytolytic HIV-Specific CD8+ T-Cell Population in Elite Controllers. |
| 1440 | 25883386 | Here we assessed coexpression of PD-1, Lag-3, CD160, and 2B4 as a measure of T-cell exhaustion in a cohort of elite controllers and in chronic progressors. |
| 1441 | 25883386 | We found that elite controllers have a high proportion of potentially exhausted (PD1(+)CD160(+)2B4(+)) HIV-specific CD8(+) T cells that is comparable to the proportion in chronic progressors. |
| 1442 | 25883386 | However, elite controllers also harbor a population of HIV-specific CD160(+)2B4(+) CD8(+) T cells that correlates with cytolytic capacity, as measured by perforin expression, a population not commonly present in chronic progressors. |
| 1443 | 25883386 | We therefore propose that coexpression of CD160 and 2B4 delineates a population of cytolytic CD8(+) T cells important for the control of HIV. |
| 1444 | 25904740 | Used alone or in combination with tumor vaccines or antibodies targeting the CTLA4 or PD1/PD-L1 pathways, blocking anti-GARP antibodies may improve the efficiency of cancer immunotherapy. |
| 1445 | 25911759 | The earliest observed Teff subsets (CD127(-)CD62L(hi)CD27(+)) are less divided than CD62L(lo) Teff and express memory genes. |
| 1446 | 25911759 | Intermediate (CD62L(lo)CD27(+)) effector subsets include the most multicytokine-producing T cells, whereas fully activated (CD62L(lo)CD27(-)) late effector cells have a terminal Teff phenotype (PD-1(+), Fas(hi), AnnexinV(+)). |
| 1447 | 25913639 | Early results from trials of PD-1/PD-L1 ligand inhibitors in nonsmall cell lung cancer are promising, with patients experiencing rapid and durable responses in the first-, second- and third-line setting as well as in combination with chemotherapy and other immune checkpoint inhibitors. |
| 1448 | 25941561 | That is, antibodies that block inhibitory receptors such as CTLA-4 and PD-1 and thus unleash antigen-specific immune responses against tumors. |
| 1449 | 25964860 | The correlation between tumor-infiltrating lymphocyte (TIL)-expression of programmed cell death ligand 1 (PD-L1) and clinical responsiveness to the PD-1 blocking antibody nivolumab implicates adaptive immune evasion mechanisms in cancer. |
| 1450 | 25968455 | Preexisting Levels of CD4 T Cells Expressing PD-1 Are Related to Overall Survival in Prostate Cancer Patients Treated with Ipilimumab. |
| 1451 | 25968455 | We found that the treatment induced an increase in the levels of CD4(+) effector T (Teff) cells, regulatory T cells, PD-1(+) CD4 Teff cells, and PD-1(+) CD8 T cells. |
| 1452 | 25968455 | Instead, low pretreatment baseline levels of PD-1(+) CD4 Teff cells were found to correlate with longer overall survival. |
| 1453 | 25968455 | Furthermore, baseline levels of PD-1(+) CD4 Teff cells from patients with shorter overall survival were higher than from cancer-free male control subjects. |
| 1454 | 25968455 | These results suggest that preexisting expression of immunologic checkpoint marker PD-1 on CD4 Teff cells may help identify patients that may benefit from ipilimumab treatment. |
| 1455 | 25968455 | Preexisting Levels of CD4 T Cells Expressing PD-1 Are Related to Overall Survival in Prostate Cancer Patients Treated with Ipilimumab. |
| 1456 | 25968455 | We found that the treatment induced an increase in the levels of CD4(+) effector T (Teff) cells, regulatory T cells, PD-1(+) CD4 Teff cells, and PD-1(+) CD8 T cells. |
| 1457 | 25968455 | Instead, low pretreatment baseline levels of PD-1(+) CD4 Teff cells were found to correlate with longer overall survival. |
| 1458 | 25968455 | Furthermore, baseline levels of PD-1(+) CD4 Teff cells from patients with shorter overall survival were higher than from cancer-free male control subjects. |
| 1459 | 25968455 | These results suggest that preexisting expression of immunologic checkpoint marker PD-1 on CD4 Teff cells may help identify patients that may benefit from ipilimumab treatment. |
| 1460 | 25968455 | Preexisting Levels of CD4 T Cells Expressing PD-1 Are Related to Overall Survival in Prostate Cancer Patients Treated with Ipilimumab. |
| 1461 | 25968455 | We found that the treatment induced an increase in the levels of CD4(+) effector T (Teff) cells, regulatory T cells, PD-1(+) CD4 Teff cells, and PD-1(+) CD8 T cells. |
| 1462 | 25968455 | Instead, low pretreatment baseline levels of PD-1(+) CD4 Teff cells were found to correlate with longer overall survival. |
| 1463 | 25968455 | Furthermore, baseline levels of PD-1(+) CD4 Teff cells from patients with shorter overall survival were higher than from cancer-free male control subjects. |
| 1464 | 25968455 | These results suggest that preexisting expression of immunologic checkpoint marker PD-1 on CD4 Teff cells may help identify patients that may benefit from ipilimumab treatment. |
| 1465 | 25968455 | Preexisting Levels of CD4 T Cells Expressing PD-1 Are Related to Overall Survival in Prostate Cancer Patients Treated with Ipilimumab. |
| 1466 | 25968455 | We found that the treatment induced an increase in the levels of CD4(+) effector T (Teff) cells, regulatory T cells, PD-1(+) CD4 Teff cells, and PD-1(+) CD8 T cells. |
| 1467 | 25968455 | Instead, low pretreatment baseline levels of PD-1(+) CD4 Teff cells were found to correlate with longer overall survival. |
| 1468 | 25968455 | Furthermore, baseline levels of PD-1(+) CD4 Teff cells from patients with shorter overall survival were higher than from cancer-free male control subjects. |
| 1469 | 25968455 | These results suggest that preexisting expression of immunologic checkpoint marker PD-1 on CD4 Teff cells may help identify patients that may benefit from ipilimumab treatment. |
| 1470 | 25968455 | Preexisting Levels of CD4 T Cells Expressing PD-1 Are Related to Overall Survival in Prostate Cancer Patients Treated with Ipilimumab. |
| 1471 | 25968455 | We found that the treatment induced an increase in the levels of CD4(+) effector T (Teff) cells, regulatory T cells, PD-1(+) CD4 Teff cells, and PD-1(+) CD8 T cells. |
| 1472 | 25968455 | Instead, low pretreatment baseline levels of PD-1(+) CD4 Teff cells were found to correlate with longer overall survival. |
| 1473 | 25968455 | Furthermore, baseline levels of PD-1(+) CD4 Teff cells from patients with shorter overall survival were higher than from cancer-free male control subjects. |
| 1474 | 25968455 | These results suggest that preexisting expression of immunologic checkpoint marker PD-1 on CD4 Teff cells may help identify patients that may benefit from ipilimumab treatment. |
| 1475 | 25979549 | Interest in breast cancer immunotherapy has been reignited by recent reports of objective responses in metastatic triple-negative breast cancer with both pembrolizumab (a programmed cell death protein 1 [PD-1] antagonist) and MPDL3280A (a programmed cell death ligand 1 [PD-L1] antagonist). |
| 1476 | 26034905 | We show that the gut and female reproductive tract (FRT) of humanized DRAG mice have a high level of human lymphocytes and a high frequency of TFH (CXCR5(+)PD-1(++)) and precursor-TFH (CXCR5(+)PD-1(+)) cells. |
| 1477 | 26034905 | The majority of TFH-cells expressed CCR5 and CXCR3 and are the most permissive to HIV-1 infection. |
| 1478 | 26050634 | These successful approaches include blockade of immunosuppressive molecules like PD-1 and CTLA-4, adoptive transfer of patient derived and genetically modified T-cells, and vaccines that stimulate tumor antigen specific T-cells. |
| 1479 | 26113847 | As the co-regulatory receptors PD-1, Tim-3, and 2B4 have all been shown to be vital in regulating CD8(+) T cell function, we assessed their expression on CMV/EBV-specific CD8(+) T cells from patients with chronic hepatitis C (CHC) and healthy controls ex vivo and upon stimulation with virus-specific peptides in vitro. |
| 1480 | 26113847 | Total and CMV/EBV-specific CD8(+) T cells expressing PD-1, Tim-3, and 2B4 were highly enriched in patients with CHC compared to healthy individuals ex vivo. |
| 1481 | 26113847 | In vitro peptide stimulation further potentiated the differential co-regulatory receptor expression of PD-1, Tim-3, and 2B4, which then culminated in an enhanced functionality of CMV/EBV-specific CD8(+) T cells in CHC patients. |
| 1482 | 26113847 | Comprehensively analyzing plasma cytokines between the two cohorts, we observed that not only was IFNα-2a dominant among 21 other inflammatory mediators elevated in CHC patients but it also correlated with PD-1 and Tim-3 expressions ex vivo. |
| 1483 | 26113847 | As the co-regulatory receptors PD-1, Tim-3, and 2B4 have all been shown to be vital in regulating CD8(+) T cell function, we assessed their expression on CMV/EBV-specific CD8(+) T cells from patients with chronic hepatitis C (CHC) and healthy controls ex vivo and upon stimulation with virus-specific peptides in vitro. |
| 1484 | 26113847 | Total and CMV/EBV-specific CD8(+) T cells expressing PD-1, Tim-3, and 2B4 were highly enriched in patients with CHC compared to healthy individuals ex vivo. |
| 1485 | 26113847 | In vitro peptide stimulation further potentiated the differential co-regulatory receptor expression of PD-1, Tim-3, and 2B4, which then culminated in an enhanced functionality of CMV/EBV-specific CD8(+) T cells in CHC patients. |
| 1486 | 26113847 | Comprehensively analyzing plasma cytokines between the two cohorts, we observed that not only was IFNα-2a dominant among 21 other inflammatory mediators elevated in CHC patients but it also correlated with PD-1 and Tim-3 expressions ex vivo. |
| 1487 | 26113847 | As the co-regulatory receptors PD-1, Tim-3, and 2B4 have all been shown to be vital in regulating CD8(+) T cell function, we assessed their expression on CMV/EBV-specific CD8(+) T cells from patients with chronic hepatitis C (CHC) and healthy controls ex vivo and upon stimulation with virus-specific peptides in vitro. |
| 1488 | 26113847 | Total and CMV/EBV-specific CD8(+) T cells expressing PD-1, Tim-3, and 2B4 were highly enriched in patients with CHC compared to healthy individuals ex vivo. |
| 1489 | 26113847 | In vitro peptide stimulation further potentiated the differential co-regulatory receptor expression of PD-1, Tim-3, and 2B4, which then culminated in an enhanced functionality of CMV/EBV-specific CD8(+) T cells in CHC patients. |
| 1490 | 26113847 | Comprehensively analyzing plasma cytokines between the two cohorts, we observed that not only was IFNα-2a dominant among 21 other inflammatory mediators elevated in CHC patients but it also correlated with PD-1 and Tim-3 expressions ex vivo. |
| 1491 | 26113847 | As the co-regulatory receptors PD-1, Tim-3, and 2B4 have all been shown to be vital in regulating CD8(+) T cell function, we assessed their expression on CMV/EBV-specific CD8(+) T cells from patients with chronic hepatitis C (CHC) and healthy controls ex vivo and upon stimulation with virus-specific peptides in vitro. |
| 1492 | 26113847 | Total and CMV/EBV-specific CD8(+) T cells expressing PD-1, Tim-3, and 2B4 were highly enriched in patients with CHC compared to healthy individuals ex vivo. |
| 1493 | 26113847 | In vitro peptide stimulation further potentiated the differential co-regulatory receptor expression of PD-1, Tim-3, and 2B4, which then culminated in an enhanced functionality of CMV/EBV-specific CD8(+) T cells in CHC patients. |
| 1494 | 26113847 | Comprehensively analyzing plasma cytokines between the two cohorts, we observed that not only was IFNα-2a dominant among 21 other inflammatory mediators elevated in CHC patients but it also correlated with PD-1 and Tim-3 expressions ex vivo. |
| 1495 | 26116499 | CD4 T Cell Depletion Substantially Augments the Rescue Potential of PD-L1 Blockade for Deeply Exhausted CD8 T Cells. |
| 1496 | 26116499 | In a model of chronic lymphocytic choriomeningitis virus infection in mice, we show that exhausted CD8 T cells during the late stage of infection are refractory to rescue by PD-L1 blockade. |
| 1497 | 26116499 | Interestingly, PD-L1 blockade during the late stage of infection resulted in a biased expansion of PD-1(+) CTLA-4(+) regulatory T cells (Tregs) over antiviral CD8 T cells. |
| 1498 | 26116499 | In this report, we show that PD-L1 blockade together with CD4 T cell depletion effectively rescued deeply exhausted CD8 T cells and enhanced antiviral control during the late stage of chronic infection without any associated mortality. |
| 1499 | 26116499 | These data demonstrate the pleiotropic effects of anti-PD-L1 therapy on both virus-specific CD8 T cells and Tregs, and suggest a novel strategy for effectively rescuing deeply exhausted CD8 T cells. |
| 1500 | 26122553 | Performance status, injection site skin reaction and circulating PD-1(+) CD4(+) T-cells were significantly prognostic of overall survival, and multivariate analysis also indicated that the performance status and circulating PD-1(+) CD4(+) T-cells were prognostic. |
| 1501 | 26155422 | Interferon-γ-induced activation of JAK1 and JAK2 suppresses tumor cell susceptibility to NK cells through upregulation of PD-L1 expression. |
| 1502 | 26155422 | Inhibition of JAK1 or JAK2 in human tumor cells was previously shown to increase susceptibility of these cells to NK cell lysis. |
| 1503 | 26155422 | Incubation of tumor cells with supernatant from activated NK cells or interferon-gamma (IFNγ)-induced activation of pSTAT1 and increased expression of PD-L1 without altering expression of other activating or inhibitory NK cell ligands. |
| 1504 | 26155422 | These functional effects were blocked by chemical JAK inhibition or shRNAs targeting JAK1, JAK2 or STAT1. |
| 1505 | 26155422 | These results show that NK cell activation and secretion of IFNγ results in activation of JAK1, JAK2 and STAT1 in tumor cells, resulting in rapid up-regulation of PD-L1 expression. |
| 1506 | 26155422 | These observations suggest that JAK pathway inhibitors as well as PD-1 and PD-L1 antibodies may work synergistically with other immune therapies by preventing IFN-induced inhibition of NK cell-mediated tumor cell lysis. |
| 1507 | 26177645 | Immune checkpoint inhibitors such as ipilimumab, anti-PD-1 monoclonal antibody (programmed cell death-1), and Indoleamine 2,3-dioxygenase (IDO) inhibitors have shown some promise in this field. |
| 1508 | 26211834 | Tim-3 and Tim-4 as the potential targets for antitumor therapy. |
| 1509 | 26211834 | Both Tim-3 and Tim-4 belong to the T-cell immunoglobulin and mucin domain (Tim) gene family, which plays a critical role in immunoregulation. |
| 1510 | 26211834 | Recently, data from experimental models of tumor discovered that Tim-3 and Tim-4 up-regulation on tumor associated dendritic cells and macrophages attenuated the anti-tumor effects of cancer vaccines and chemotherapy. |
| 1511 | 26211834 | Moreover, co-blockage of Tim-3 and PD-1, Tim-3 and CD137, Tim-3 and carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) could enhance cell-mediated immunity in advanced tumor, and combined treatment with anti-Tim-3 and anti-Tim-4 mAbs further increase the efficacy of cancer vaccines. |
| 1512 | 26211834 | The therapeutic manipulation of TIM-3 and TIM-4 may provide a novel strategy to improve the clinical efficacy of cancer immunotherapy. |
| 1513 | 26216629 | Most of the current immunotherapeutic success in cancer treatment is based on the use of immune-modulating antibodies targeting critical checkpoints (CTLA-4 and PD-1/PD-L1). |
| 1514 | 26221072 | Higher Frequency of Circulating PD-1(high) CXCR5(+)CD4(+) Tfh Cells in Patients with Chronic Schistosomiasis. |
| 1515 | 26221072 | Significantly higher frequencies of circulating CXCR5(+) CD4(+) Tfh cells and higher expression levels of ICOS and PD-1 in CXCR5(+) CD4(+) Tfh cells were observed in patients with chronic schistosomiasis compared to HC. |
| 1516 | 26221072 | Moreover, the frequency of circulating PD-1(high) CXCR5(+) CD4(+) Tfh cells positively correlated with the levels of IL-21 in serum from patients with chronic schistosomiasis. |
| 1517 | 26221072 | A positive correlation was also found between the frequency of PD-1(high) CXCR5(+) CD4(+) Tfh cells and the levels of soluble egg antigen (SEA)-specific antibodies in serum samples from the patient group. |
| 1518 | 26221072 | Our study is the first regarding Tfh cells in chronic human schistosomiasis and the finding indicate that PD-1(high) CXCR5(+) CD4(+)Tfh cells might play an important role in the production of specific antibodies in schistosomiasis. |
| 1519 | 26221072 | Higher Frequency of Circulating PD-1(high) CXCR5(+)CD4(+) Tfh Cells in Patients with Chronic Schistosomiasis. |
| 1520 | 26221072 | Significantly higher frequencies of circulating CXCR5(+) CD4(+) Tfh cells and higher expression levels of ICOS and PD-1 in CXCR5(+) CD4(+) Tfh cells were observed in patients with chronic schistosomiasis compared to HC. |
| 1521 | 26221072 | Moreover, the frequency of circulating PD-1(high) CXCR5(+) CD4(+) Tfh cells positively correlated with the levels of IL-21 in serum from patients with chronic schistosomiasis. |
| 1522 | 26221072 | A positive correlation was also found between the frequency of PD-1(high) CXCR5(+) CD4(+) Tfh cells and the levels of soluble egg antigen (SEA)-specific antibodies in serum samples from the patient group. |
| 1523 | 26221072 | Our study is the first regarding Tfh cells in chronic human schistosomiasis and the finding indicate that PD-1(high) CXCR5(+) CD4(+)Tfh cells might play an important role in the production of specific antibodies in schistosomiasis. |
| 1524 | 26221072 | Higher Frequency of Circulating PD-1(high) CXCR5(+)CD4(+) Tfh Cells in Patients with Chronic Schistosomiasis. |
| 1525 | 26221072 | Significantly higher frequencies of circulating CXCR5(+) CD4(+) Tfh cells and higher expression levels of ICOS and PD-1 in CXCR5(+) CD4(+) Tfh cells were observed in patients with chronic schistosomiasis compared to HC. |
| 1526 | 26221072 | Moreover, the frequency of circulating PD-1(high) CXCR5(+) CD4(+) Tfh cells positively correlated with the levels of IL-21 in serum from patients with chronic schistosomiasis. |
| 1527 | 26221072 | A positive correlation was also found between the frequency of PD-1(high) CXCR5(+) CD4(+) Tfh cells and the levels of soluble egg antigen (SEA)-specific antibodies in serum samples from the patient group. |
| 1528 | 26221072 | Our study is the first regarding Tfh cells in chronic human schistosomiasis and the finding indicate that PD-1(high) CXCR5(+) CD4(+)Tfh cells might play an important role in the production of specific antibodies in schistosomiasis. |
| 1529 | 26221072 | Higher Frequency of Circulating PD-1(high) CXCR5(+)CD4(+) Tfh Cells in Patients with Chronic Schistosomiasis. |
| 1530 | 26221072 | Significantly higher frequencies of circulating CXCR5(+) CD4(+) Tfh cells and higher expression levels of ICOS and PD-1 in CXCR5(+) CD4(+) Tfh cells were observed in patients with chronic schistosomiasis compared to HC. |
| 1531 | 26221072 | Moreover, the frequency of circulating PD-1(high) CXCR5(+) CD4(+) Tfh cells positively correlated with the levels of IL-21 in serum from patients with chronic schistosomiasis. |
| 1532 | 26221072 | A positive correlation was also found between the frequency of PD-1(high) CXCR5(+) CD4(+) Tfh cells and the levels of soluble egg antigen (SEA)-specific antibodies in serum samples from the patient group. |
| 1533 | 26221072 | Our study is the first regarding Tfh cells in chronic human schistosomiasis and the finding indicate that PD-1(high) CXCR5(+) CD4(+)Tfh cells might play an important role in the production of specific antibodies in schistosomiasis. |
| 1534 | 26221072 | Higher Frequency of Circulating PD-1(high) CXCR5(+)CD4(+) Tfh Cells in Patients with Chronic Schistosomiasis. |
| 1535 | 26221072 | Significantly higher frequencies of circulating CXCR5(+) CD4(+) Tfh cells and higher expression levels of ICOS and PD-1 in CXCR5(+) CD4(+) Tfh cells were observed in patients with chronic schistosomiasis compared to HC. |
| 1536 | 26221072 | Moreover, the frequency of circulating PD-1(high) CXCR5(+) CD4(+) Tfh cells positively correlated with the levels of IL-21 in serum from patients with chronic schistosomiasis. |
| 1537 | 26221072 | A positive correlation was also found between the frequency of PD-1(high) CXCR5(+) CD4(+) Tfh cells and the levels of soluble egg antigen (SEA)-specific antibodies in serum samples from the patient group. |
| 1538 | 26221072 | Our study is the first regarding Tfh cells in chronic human schistosomiasis and the finding indicate that PD-1(high) CXCR5(+) CD4(+)Tfh cells might play an important role in the production of specific antibodies in schistosomiasis. |
| 1539 | 26230145 | Variants that enhanced interferon-gamma (IFN-γ) and/or interleukin-2 (IL-2) production in enzyme-linked immunospot assays (29 cases overall) were subsequently tested by 7-day in vitro peptide stimulation for their effects on HIV-specific CD8(+) T cell proliferation and programmed death-1 (PD-1) expression. |
| 1540 | 26230145 | Heteroclitic variants enhanced HIV-specific CD8(+) T cell proliferation by >20% in 13/29 cases tested, reduced PD-1 expression on proliferating cells by 15-50% in 10 cases, and reduced PD-1 expression on proliferating cells by >50% in 3 cases. |
| 1541 | 26230145 | Variants that enhanced interferon-gamma (IFN-γ) and/or interleukin-2 (IL-2) production in enzyme-linked immunospot assays (29 cases overall) were subsequently tested by 7-day in vitro peptide stimulation for their effects on HIV-specific CD8(+) T cell proliferation and programmed death-1 (PD-1) expression. |
| 1542 | 26230145 | Heteroclitic variants enhanced HIV-specific CD8(+) T cell proliferation by >20% in 13/29 cases tested, reduced PD-1 expression on proliferating cells by 15-50% in 10 cases, and reduced PD-1 expression on proliferating cells by >50% in 3 cases. |
| 1543 | 26261892 | However, anticancer CTLs can be inhibited by several immune inhibitory mechanisms, including the interaction between programmed death 1 (PD-1) and its ligand PD-L1, on T cells and cancer cells, respectively. |
| 1544 | 26261892 | Such PD-L1 peptide-stimulated CD8 T cells showed cytotoxicity against HLA-A24(+) and PD-L1-expressing RCC cells. |
| 1545 | 26261892 | Although IFN-γ treatment increased PD-L1 expression on PD-L1(low) RCC cells, their sensitivity to cytotoxicity of PD-L1 peptide-stimulated CD8(+) T cells varied between patients. |
| 1546 | 26297764 | TFR are natural regulatory T cells (TREG) that migrate into the follicle and, similar to TFH, upregulate CXCR5, Bcl-6, and PD1. |
| 1547 | 26297764 | In this study, we identified TFR as CD4(+)CD25(+)FOXP3(+)CXCR5(+)PD1(hi)Bcl-6(+) within lymph nodes of rhesus macaques (RM) and confirmed their localization within the GC by immunohistochemistry. |
| 1548 | 26297764 | RNA sequencing showed that TFR exhibit a distinct transcriptional profile with shared features of both TFH and TREG, including intermediate expression of FOXP3, Bcl-6, PRDM1, IL-10, and IL-21. |
| 1549 | 26297764 | TFR are natural regulatory T cells (TREG) that migrate into the follicle and, similar to TFH, upregulate CXCR5, Bcl-6, and PD1. |
| 1550 | 26297764 | In this study, we identified TFR as CD4(+)CD25(+)FOXP3(+)CXCR5(+)PD1(hi)Bcl-6(+) within lymph nodes of rhesus macaques (RM) and confirmed their localization within the GC by immunohistochemistry. |
| 1551 | 26297764 | RNA sequencing showed that TFR exhibit a distinct transcriptional profile with shared features of both TFH and TREG, including intermediate expression of FOXP3, Bcl-6, PRDM1, IL-10, and IL-21. |
| 1552 | 26301204 | Monoclonal antibody therapies against tumor antigens such as disialoganglioside GD2 or immune checkpoint targets such as CTLA-4 and PD-1 are being actively explored in pediatric sarcomas. |
| 1553 | 26333070 | Using CXCR5, CXCR3, CCR6, CCR7, PD1, and ICOS as markers, Tfh-like cells can be identified in the circulation and be classified into three functionally distinct subsets that are PD1+ICOS+, PD1+ ICOS-, or PD1-ICOS-. |
| 1554 | 26333070 | We used these markers to identify different subsets of CXCR5+CD4+ Tfh-like cells in response to highly immunogenic and efficacious vaccines for human papillomaviruses (HPV): Cervarix and Gardasil. |
| 1555 | 26333070 | PD1+ICOS+ CXCR3+CCR6-CXCR5+CD4+ (Tfh1-like) cells were induced and peaked on Day (D) 7 post-first vaccination, but not as much on D7 post-third vaccination. |
| 1556 | 26333070 | We also observed a trend toward increase in PD1+ICOS+ CXCR3-CCR6-CXCR5+CD4+ (Tfh2-like) cells for both vaccines, and PD1+ICOS+ CXCR3-CCR6+CXCR5+CD4+ (Tfh17-like) subset was induced by Cervarix post-first vaccination. |
| 1557 | 26333070 | We found frequencies of memory B cells at D30 correlated with anti-HPV16 and 18 antibody titers from D30, and the induction levels of memory B cells at D30 and PD1+ICOS+Tfh1-like cells at D7 post-first vaccination correlated for Cervarix. |
| 1558 | 26333070 | Our study showed that induction of circulating CXCR5+CD4+ Tfh-like subsets can be detected following immunization with HPV vaccines, and potentially be useful as a marker of immunogenicity of vaccines. |
| 1559 | 26333070 | Using CXCR5, CXCR3, CCR6, CCR7, PD1, and ICOS as markers, Tfh-like cells can be identified in the circulation and be classified into three functionally distinct subsets that are PD1+ICOS+, PD1+ ICOS-, or PD1-ICOS-. |
| 1560 | 26333070 | We used these markers to identify different subsets of CXCR5+CD4+ Tfh-like cells in response to highly immunogenic and efficacious vaccines for human papillomaviruses (HPV): Cervarix and Gardasil. |
| 1561 | 26333070 | PD1+ICOS+ CXCR3+CCR6-CXCR5+CD4+ (Tfh1-like) cells were induced and peaked on Day (D) 7 post-first vaccination, but not as much on D7 post-third vaccination. |
| 1562 | 26333070 | We also observed a trend toward increase in PD1+ICOS+ CXCR3-CCR6-CXCR5+CD4+ (Tfh2-like) cells for both vaccines, and PD1+ICOS+ CXCR3-CCR6+CXCR5+CD4+ (Tfh17-like) subset was induced by Cervarix post-first vaccination. |
| 1563 | 26333070 | We found frequencies of memory B cells at D30 correlated with anti-HPV16 and 18 antibody titers from D30, and the induction levels of memory B cells at D30 and PD1+ICOS+Tfh1-like cells at D7 post-first vaccination correlated for Cervarix. |
| 1564 | 26333070 | Our study showed that induction of circulating CXCR5+CD4+ Tfh-like subsets can be detected following immunization with HPV vaccines, and potentially be useful as a marker of immunogenicity of vaccines. |
| 1565 | 26333070 | Using CXCR5, CXCR3, CCR6, CCR7, PD1, and ICOS as markers, Tfh-like cells can be identified in the circulation and be classified into three functionally distinct subsets that are PD1+ICOS+, PD1+ ICOS-, or PD1-ICOS-. |
| 1566 | 26333070 | We used these markers to identify different subsets of CXCR5+CD4+ Tfh-like cells in response to highly immunogenic and efficacious vaccines for human papillomaviruses (HPV): Cervarix and Gardasil. |
| 1567 | 26333070 | PD1+ICOS+ CXCR3+CCR6-CXCR5+CD4+ (Tfh1-like) cells were induced and peaked on Day (D) 7 post-first vaccination, but not as much on D7 post-third vaccination. |
| 1568 | 26333070 | We also observed a trend toward increase in PD1+ICOS+ CXCR3-CCR6-CXCR5+CD4+ (Tfh2-like) cells for both vaccines, and PD1+ICOS+ CXCR3-CCR6+CXCR5+CD4+ (Tfh17-like) subset was induced by Cervarix post-first vaccination. |
| 1569 | 26333070 | We found frequencies of memory B cells at D30 correlated with anti-HPV16 and 18 antibody titers from D30, and the induction levels of memory B cells at D30 and PD1+ICOS+Tfh1-like cells at D7 post-first vaccination correlated for Cervarix. |
| 1570 | 26333070 | Our study showed that induction of circulating CXCR5+CD4+ Tfh-like subsets can be detected following immunization with HPV vaccines, and potentially be useful as a marker of immunogenicity of vaccines. |
| 1571 | 26333070 | Using CXCR5, CXCR3, CCR6, CCR7, PD1, and ICOS as markers, Tfh-like cells can be identified in the circulation and be classified into three functionally distinct subsets that are PD1+ICOS+, PD1+ ICOS-, or PD1-ICOS-. |
| 1572 | 26333070 | We used these markers to identify different subsets of CXCR5+CD4+ Tfh-like cells in response to highly immunogenic and efficacious vaccines for human papillomaviruses (HPV): Cervarix and Gardasil. |
| 1573 | 26333070 | PD1+ICOS+ CXCR3+CCR6-CXCR5+CD4+ (Tfh1-like) cells were induced and peaked on Day (D) 7 post-first vaccination, but not as much on D7 post-third vaccination. |
| 1574 | 26333070 | We also observed a trend toward increase in PD1+ICOS+ CXCR3-CCR6-CXCR5+CD4+ (Tfh2-like) cells for both vaccines, and PD1+ICOS+ CXCR3-CCR6+CXCR5+CD4+ (Tfh17-like) subset was induced by Cervarix post-first vaccination. |
| 1575 | 26333070 | We found frequencies of memory B cells at D30 correlated with anti-HPV16 and 18 antibody titers from D30, and the induction levels of memory B cells at D30 and PD1+ICOS+Tfh1-like cells at D7 post-first vaccination correlated for Cervarix. |
| 1576 | 26333070 | Our study showed that induction of circulating CXCR5+CD4+ Tfh-like subsets can be detected following immunization with HPV vaccines, and potentially be useful as a marker of immunogenicity of vaccines. |
| 1577 | 26337747 | An HPV-E6/E7 immunotherapy plus PD-1 checkpoint inhibition results in tumor regression and reduction in PD-L1 expression. |
| 1578 | 26337747 | Analysis of the tumor microenvironment in Ad5 [E1-, E2b-]-E6/E7 treated mice revealed elevated CD8(+) tumor infiltrating lymphocytes (TILs); however, we observed induction of suppressive mechanisms such as programmed death-ligand 1 (PD-L1) expression on tumor cells and an increase in PD-1(+) TILs. |
| 1579 | 26337747 | When Ad5 [E1-, E2b-]-E6/E7 immunotherapy was combined with anti-PD-1 antibody, we observed CD8(+) TILs at the same level but a reduction in tumor PD-L1 expression on tumor cells and reduced PD-1(+) TILs providing a mechanism by which combination therapy favors a tumor clearance state and a rationale for pairing antigen-specific vaccines with checkpoint inhibitors in future clinical trials. |
| 1580 | 26337747 | An HPV-E6/E7 immunotherapy plus PD-1 checkpoint inhibition results in tumor regression and reduction in PD-L1 expression. |
| 1581 | 26337747 | Analysis of the tumor microenvironment in Ad5 [E1-, E2b-]-E6/E7 treated mice revealed elevated CD8(+) tumor infiltrating lymphocytes (TILs); however, we observed induction of suppressive mechanisms such as programmed death-ligand 1 (PD-L1) expression on tumor cells and an increase in PD-1(+) TILs. |
| 1582 | 26337747 | When Ad5 [E1-, E2b-]-E6/E7 immunotherapy was combined with anti-PD-1 antibody, we observed CD8(+) TILs at the same level but a reduction in tumor PD-L1 expression on tumor cells and reduced PD-1(+) TILs providing a mechanism by which combination therapy favors a tumor clearance state and a rationale for pairing antigen-specific vaccines with checkpoint inhibitors in future clinical trials. |
| 1583 | 26337747 | An HPV-E6/E7 immunotherapy plus PD-1 checkpoint inhibition results in tumor regression and reduction in PD-L1 expression. |
| 1584 | 26337747 | Analysis of the tumor microenvironment in Ad5 [E1-, E2b-]-E6/E7 treated mice revealed elevated CD8(+) tumor infiltrating lymphocytes (TILs); however, we observed induction of suppressive mechanisms such as programmed death-ligand 1 (PD-L1) expression on tumor cells and an increase in PD-1(+) TILs. |
| 1585 | 26337747 | When Ad5 [E1-, E2b-]-E6/E7 immunotherapy was combined with anti-PD-1 antibody, we observed CD8(+) TILs at the same level but a reduction in tumor PD-L1 expression on tumor cells and reduced PD-1(+) TILs providing a mechanism by which combination therapy favors a tumor clearance state and a rationale for pairing antigen-specific vaccines with checkpoint inhibitors in future clinical trials. |
| 1586 | 26366739 | Absence of protective immunity during acute malaria correlated with maintenance of antibodies to NTS, but a marked reduction in effector capability of Salmonella-specific CD4 and CD8 T cells. |
| 1587 | 26366739 | Further, increased expression of the inhibitory molecule PD1 was identified on memory CD4 T cells induced by vaccination. |
| 1588 | 26366739 | Simultaneous blockade of CTLA-4, LAG3, and PDL1 restored IFN-γ production by vaccine-induced memory CD4 T cells but was not sufficient to restore protection. |
| 1589 | 26376844 | The development of new immunomodulatory monoclonal antibodies targeting the CTLA-4 or PD-1 axis has led to a revival of research on immunotherapies in solid tumours including renal cell cancer (RCC). |
| 1590 | 26376844 | However, at the moment there is no evidence that targeting the CTLA-4 or PD-1 axis provides a substantial clinical benefit compared to established treatment with tyrosine kinase or mTOR inhibitors. |
| 1591 | 26376844 | In this chapter we will summarise selected studies on immunotherapy in advanced RCC with a focus on anti-PD-1, anti-PD-L1, and anti-CTLA-4 antibodies. |
| 1592 | 26376844 | The development of new immunomodulatory monoclonal antibodies targeting the CTLA-4 or PD-1 axis has led to a revival of research on immunotherapies in solid tumours including renal cell cancer (RCC). |
| 1593 | 26376844 | However, at the moment there is no evidence that targeting the CTLA-4 or PD-1 axis provides a substantial clinical benefit compared to established treatment with tyrosine kinase or mTOR inhibitors. |
| 1594 | 26376844 | In this chapter we will summarise selected studies on immunotherapy in advanced RCC with a focus on anti-PD-1, anti-PD-L1, and anti-CTLA-4 antibodies. |
| 1595 | 26377033 | We show that codelivery of IL-12 by VSV-G-LVs or DC2.1-LVs augments CD4(+) or CD8(+) T-cell proliferation, respectively. |
| 1596 | 26377033 | Furthermore, we demonstrate that codelivery of IL-12 enhances the CD4(+) TH 1 profile irrespective of its delivery mode, while an increase in cytotoxic and therapeutic CD8(+) T cells was only induced upon VSV-G-LV injection. |
| 1597 | 26377033 | While codelivery of IL-12 by DC2.1-LVs did not enhance CD8(+) T-cell performance, it increased expression of inhibitory checkpoint markers Lag3, Tim3, and PD-1. |
| 1598 | 26377033 | Finally, the discrepancy between CD4(+) T-cell stimulation with and without functional CD8(+) T-cell stimulation by VSV-G- and DC2.1-LVs is partly explained by the observation that IL-12 relieves CD8(+) T cells from CD4(+) T-cell help, implying that a T(H)1 profile is of minor importance for antitumor immunotherapy if IL-12 is exogenously delivered. |
| 1599 | 26378990 | In the current study, we investigated the role of programmed death (PD)-1 and its ligands PD-L1 and PD-L2 in promoting early-life Chlamydia respiratory infection, and infection-induced airway hyperresponsiveness (AHR) and severe allergic airway disease in later life. |
| 1600 | 26378990 | Infection increased PD-1 and PD-L1, but not PD-L2, mRNA expression in the lung. |
| 1601 | 26378990 | Flow cytometric analysis of whole lung homogenates identified monocytes, dendritic cells, CD4(+), and CD8(+) T cells as major sources of PD-1 and PD-L1. |
| 1602 | 26378990 | Inhibition of PD-1 and PD-L1, but not PD-L2, during infection ablated infection-induced AHR in later life. |
| 1603 | 26378990 | Infection decreased the levels of the IL-13 decoy receptor in the lung, which were restored to baseline levels by inhibition of PD-L1. |
| 1604 | 26378990 | Finally, inhibition of PD-L1 during infection prevented subsequent infection-induced severe allergic airways disease in later life by decreasing IL-13 levels, Gob-5 expression, mucus production, and AHR. |
| 1605 | 26378990 | In the current study, we investigated the role of programmed death (PD)-1 and its ligands PD-L1 and PD-L2 in promoting early-life Chlamydia respiratory infection, and infection-induced airway hyperresponsiveness (AHR) and severe allergic airway disease in later life. |
| 1606 | 26378990 | Infection increased PD-1 and PD-L1, but not PD-L2, mRNA expression in the lung. |
| 1607 | 26378990 | Flow cytometric analysis of whole lung homogenates identified monocytes, dendritic cells, CD4(+), and CD8(+) T cells as major sources of PD-1 and PD-L1. |
| 1608 | 26378990 | Inhibition of PD-1 and PD-L1, but not PD-L2, during infection ablated infection-induced AHR in later life. |
| 1609 | 26378990 | Infection decreased the levels of the IL-13 decoy receptor in the lung, which were restored to baseline levels by inhibition of PD-L1. |
| 1610 | 26378990 | Finally, inhibition of PD-L1 during infection prevented subsequent infection-induced severe allergic airways disease in later life by decreasing IL-13 levels, Gob-5 expression, mucus production, and AHR. |
| 1611 | 26378990 | In the current study, we investigated the role of programmed death (PD)-1 and its ligands PD-L1 and PD-L2 in promoting early-life Chlamydia respiratory infection, and infection-induced airway hyperresponsiveness (AHR) and severe allergic airway disease in later life. |
| 1612 | 26378990 | Infection increased PD-1 and PD-L1, but not PD-L2, mRNA expression in the lung. |
| 1613 | 26378990 | Flow cytometric analysis of whole lung homogenates identified monocytes, dendritic cells, CD4(+), and CD8(+) T cells as major sources of PD-1 and PD-L1. |
| 1614 | 26378990 | Inhibition of PD-1 and PD-L1, but not PD-L2, during infection ablated infection-induced AHR in later life. |
| 1615 | 26378990 | Infection decreased the levels of the IL-13 decoy receptor in the lung, which were restored to baseline levels by inhibition of PD-L1. |
| 1616 | 26378990 | Finally, inhibition of PD-L1 during infection prevented subsequent infection-induced severe allergic airways disease in later life by decreasing IL-13 levels, Gob-5 expression, mucus production, and AHR. |
| 1617 | 26379242 | Programed death-ligand 2 (PD-L2), expressed both on B and the highly activated CD4high T cells, contributed to the increase of interferon-γ recall response through a PD1-independent pathway. |
| 1618 | 26379242 | We also invite to consider B cells, PD-L2 and PI3K as potential targets for therapeutic modulation of T cell cytokine responses for tuberculosis control. |
| 1619 | 26431275 | Through antigen spreading these animals also developed tumor-specific cytotoxic CD8+ T cells, but neither CD4+ T cells nor antibodies, rejecting WT-AB1 mesothelioma. |
| 1620 | 26431275 | Adoptive cell transfer experiments further demonstrated that antigen spreading-induced CD8+ T cells conferred efficacious therapeutic effects against established WT-AB1 mesothelioma and prevented the increase of exhausted PD-1+ and Tim-3+ CD8+ T cells. |
| 1621 | 26431275 | A significant inverse correlation was found between the frequency of functional PD1-Tim3- CD8+ T cells and that of MDSCs or tumor mass in vivo. |
| 1622 | 26431275 | Through antigen spreading these animals also developed tumor-specific cytotoxic CD8+ T cells, but neither CD4+ T cells nor antibodies, rejecting WT-AB1 mesothelioma. |
| 1623 | 26431275 | Adoptive cell transfer experiments further demonstrated that antigen spreading-induced CD8+ T cells conferred efficacious therapeutic effects against established WT-AB1 mesothelioma and prevented the increase of exhausted PD-1+ and Tim-3+ CD8+ T cells. |
| 1624 | 26431275 | A significant inverse correlation was found between the frequency of functional PD1-Tim3- CD8+ T cells and that of MDSCs or tumor mass in vivo. |
| 1625 | 26440897 | We show that Malian children have resting PD-1(+)CXCR5(+)CD4(+) Tfh cells in circulation that resemble germinal center Tfh cells phenotypically and functionally. |
| 1626 | 26440897 | Within this population, PD-1(+)CXCR5(+)CXCR3(-) Tfh cells are superior to Th1-polarized PD-1(+)CXCR5(+)CXCR3(+) Tfh cells in helping B cells. |
| 1627 | 26440897 | We show that Malian children have resting PD-1(+)CXCR5(+)CD4(+) Tfh cells in circulation that resemble germinal center Tfh cells phenotypically and functionally. |
| 1628 | 26440897 | Within this population, PD-1(+)CXCR5(+)CXCR3(-) Tfh cells are superior to Th1-polarized PD-1(+)CXCR5(+)CXCR3(+) Tfh cells in helping B cells. |