title: Inhibition of human gamma delta [corrected] T-cell antitumoral activity through HLA-G: implications for immunotherapy of cancer.
abstract: 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.
authors.affiliation: CEAEA, I2BM, Service de Recherches en Hemato-Immunologie, 75475 Paris, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Lesport
authors.forename: Jeremy
authors.initials: J
authors.lastname: Baudhuin
authors.forename: Sylvie
authors.initials: S
authors.lastname: Sousa
authors.forename: Joel
authors.initials: J
authors.lastname: LeMaoult
authors.forename: Alessia
authors.initials: A
authors.lastname: Zamborlini
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rouas-Freiss
authors.forename: Edgardo D
authors.initials: ED
authors.lastname: Carosella
authors.forename: Benoit
authors.initials: B
authors.lastname: Favier
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis; D015153:Blotting, Western; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006680:HLA Antigens / Q000378:metabolism*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000378:metabolism; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D008213:Lymphocyte Activation / Q000276:immunology*; D008545:Melanoma / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D008562:Membrane Glycoproteins / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D054345:Receptors, KIR2DL4 / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D015703:Antigens, CD; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; C515079:KIR2DL4 protein, human; C105299:LILRB1 protein, human; C491341:LILRB2 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D008562:Membrane Glycoproteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011971:Receptors, Immunologic; D054345:Receptors, KIR2DL4; D007371:Interferon-gamma