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Inhibition of human Vγ9Vδ2 T-cell antitumoral activity through HLA-G: implications for immunotherapy of cancer

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An Erratum to this article was published on 08 June 2011

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.

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Acknowledgments

This work was supported by the Commissariat à l’Energie Atomique (CEA). J.B. is supported by an IRTELIS fellowship from CEA. We thank Helene Sicard (Innate Pharma, Marseille, France) for kindly providing BrHPP, and Niclas Setterblad and the Service Commun d’Imagerie Cellulaire et Moleculaire for their help. We also thank Nuala Mooney for helpful discussions and critical reading of the manuscript.

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Authors and Affiliations

  1. CEAEA, I2BM, Service de Recherches en Hemato-Immunologie, 75475, Paris, France

    Emilie Lesport, Jeremy Baudhuin, Sylvie Sousa, Joel LeMaoult, Nathalie Rouas-Freiss, Edgardo D. Carosella & Benoit Favier

  2. UMR_E, Université Paris Diderot, Institut Universitaire d’Hématologie, Paris, France

    Emilie Lesport, Jeremy Baudhuin, Sylvie Sousa, Joel LeMaoult, Nathalie Rouas-Freiss, Edgardo D. Carosella & Benoit Favier

  3. CNRS UMR7212, Inserm U944, Université Paris Diderot, Institut Universitaire d’Hématologie, Paris, France

    Alessia Zamborlini

  4. CEA, I2BM Service de Recherches en Hemato-Immunologie, Institut Universitaire d’Hematologie, Hopital Saint Louis, 1 Avenue Claude Vellefaux, 75010, Paris, France

    Emilie Lesport, Jeremy Baudhuin, Sylvie Sousa, Joel LeMaoult, Alessia Zamborlini, Nathalie Rouas-Freiss, Edgardo D. Carosella & Benoit Favier

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  1. Emilie Lesport
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An erratum to this article can be found at http://dx.doi.org/10.1007/s00018-011-0742-2

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Lesport, E., Baudhuin, J., Sousa, S. et al. Inhibition of human Vγ9Vδ2 T-cell antitumoral activity through HLA-G: implications for immunotherapy of cancer. Cell. Mol. Life Sci. 68, 3385–3399 (2011). https://doi.org/10.1007/s00018-011-0632-7

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