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Lesport E.,CEAEA | Lesport E.,University Paris Diderot | Lesport E.,French Atomic Energy Commission | Baudhuin J.,CEAEA | And 19 more authors.
Cellular and Molecular Life Sciences | Year: 2011

Vγ9Vδ2 T cells play a crucial role in the antitumoral immune response through cytokine production and cytotoxicity. Although the expression of the immunomodulatory molecule HLA-G has been found in diverse tumors, its impact on Vγ9Vδ2 T-cell functions remains unknown. Here we showed that soluble HLA-G inhibits Vγ9Vδ2 T-cell proliferation without inducing apoptosis. Moreover, soluble HLA-G inhibited the Vγ9Vδ2 T-cell production of IFN-γ induced by phosphoantigen stimulation. The reduction in Vγ9Vδ2 T-cell IFN-γ production was also induced by membrane-bound or soluble HLA-G expressed by tumor cell lines. Finally, primary tumor cells inhibited Vγ9Vδ2 T-cell proliferation and IFN-γ production through HLA-G. In this context, HLA-G impaired Vγ9Vδ2 T-cell cytotoxicity by interacting with ILT2 inhibitory receptor. These data demonstrate that HLA-G inhibits the anti-tumoral functions of Vγ9Vδ2 T cells and imply that treatments targeting HLA-G could optimize Vγ9Vδ2 T-cell-mediated immunotherapy of cancer. © 2011 Springer Basel AG.


PubMed | CEAEA
Type: Journal Article | Journal: Cellular and molecular life sciences : CMLS | Year: 2011

V9V2 T cells play a crucial role in the antitumoral immune response through cytokine production and cytotoxicity. Although the expression of the immunomodulatory molecule HLA-G has been found in diverse tumors, its impact on V9V2 T-cell functions remains unknown. Here we showed that soluble HLA-G inhibits V9V2 T-cell proliferation without inducing apoptosis. Moreover, soluble HLA-G inhibited the V9V2 T-cell production of IFN- induced by phosphoantigen stimulation. The reduction in V9V2 T-cell IFN- production was also induced by membrane-bound or soluble HLA-G expressed by tumor cell lines. Finally, primary tumor cells inhibited V9V2 T-cell proliferation and IFN- production through HLA-G. In this context, HLA-G impaired V9V2 T-cell cytotoxicity by interacting with ILT2 inhibitory receptor. These data demonstrate that HLA-G inhibits the anti-tumoral functions of V9V2 T cells and imply that treatments targeting HLA-G could optimize V9V2 T-cell-mediated immunotherapy of cancer.

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