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PMID |
Sentence |
1 |
16223768
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NK-cell activation by LIGHT triggers tumor-specific CD8+ T-cell immunity to reject established tumors.
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2 |
16223768
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We now demonstrate that the TNF superfamily member, LIGHT, known as TNFSF14 and a T-cell costimulatory molecule, is a critical ligand for the activation of NK cells.
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3 |
16223768
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Herpesvirus entry mediator (HVEM) is expressed on NK cells, and its engagement with LIGHT mediates NK-cell activation.
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4 |
16223768
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Interestingly, activated NK cells do not kill tumors directly but can facilitate the priming of tumor-specific CD8+ T cells in an IFN-gamma-dependent manner.
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5 |
16223768
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Conversely, intratumor depletion of either NK cells or IFN-gamma during tumor progression disrupts CD8+ cell-mediated tumor rejection, suggesting that the tumor is the essential site for the crosstalk between NK and CD8+ cells.
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6 |
16223768
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Furthermore, IFNG-deficient NK cells fail to effectively activate CD8+ T cells, suggesting IFN-gamma plays an important role in NK-mediated activation of cytotoxic T lymphocytes (CTLs).
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7 |
16223768
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Our findings establish a direct role for LIGHT in NK activation/expansion and a critical helper role of activated NK cells in priming CD8+ T cells and breaking T-cell tolerance at the tumor site.
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8 |
15115612
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LIGHT sensitizes IFN-gamma-mediated apoptosis of HT-29 human carcinoma cells through both death receptor and mitochondria pathways.
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9 |
15115612
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LIGHT [homologous to lymphotoxins, shows inducible expression, and competes with herpes simplex virus glycoprotein D for herpes virus entry mediator (HVEM/TR2)] is a new member of TNF superfamily.
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10 |
15115612
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The HT-29 colon cancer cell line is the most sensitive to LIGHT-induced, IFNg-mediated apoptosis among the cell lines we have examined so far.
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11 |
15115612
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Besides downregulation of Bcl-XL, upregulation of Bak, and activation of both PARP [poly (ADP-ribose) polymerase] and DFF45 (DNA fragmentation factor), LIGHT-induced, IFNg-mediated apoptosis of HT-29 cells involves extensive caspase activation.
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12 |
15115612
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Caspase-8 and caspase-9 activation, as shown by their cleavages appeared as early as 24 h after treatment, whereas caspase-3 and caspase-7 activation, as shown by their cleavages occurred after 72 h of LIGHT treatment.
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13 |
15115612
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Caspase-3 inhibitor Z-DEVD-FMK (benzyloxycarbonyl-Asp-Glu-Val-Asp-fluoromethylketone) and a broad range caspase inhibitor Z-VAD-FMK (benzyloxycarbonyl-Val-Ala-Asp fluoromethylketone) were able to block LIGHT-induced, IFNg-mediated apoptosis of HT-29 cells.
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14 |
15115612
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These results suggest that LIGHT-induced, IFNg-mediated apoptosis of HT-29 cells is caspase-dependent, and LIGHT signaling is mediated through both death receptor and mitochondria pathways.
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