HLA-G1 and HLA-G5 active dimers are present in malignant cells and effusions: The influence of the tumor microenvironment

Authors

  • Sonia Zilberman,

    1. CEA, IMETI, Service de Recherches en Hemato-Immunologie, Paris, France
    2. Univ Paris Diderot, Sorbonne Paris Cité, IUH, Hopital Saint-Louis, UMR_E, Paris, France
    3. Department of Obstetrics and Gynecology, Hopital Tenon, Assistance Publique des Hopitaux de Paris, CancerEst, Universite Pierre et Marie Curie (UPMC), Paris, France
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  • Chantal Schenowitz,

    1. CEA, IMETI, Service de Recherches en Hemato-Immunologie, Paris, France
    2. Univ Paris Diderot, Sorbonne Paris Cité, IUH, Hopital Saint-Louis, UMR_E, Paris, France
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  • Sophie Agaugué,

    1. CEA, IMETI, Service de Recherches en Hemato-Immunologie, Paris, France
    2. Univ Paris Diderot, Sorbonne Paris Cité, IUH, Hopital Saint-Louis, UMR_E, Paris, France
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  • Benoît Favier,

    1. CEA, IMETI, Service de Recherches en Hemato-Immunologie, Paris, France
    2. Univ Paris Diderot, Sorbonne Paris Cité, IUH, Hopital Saint-Louis, UMR_E, Paris, France
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  • Béatrice Riteau,

    1. Universite Lyon 1, Faculte de medecine RTH Laennec, CNRS FRE 3011 VirPath, Virologie et Pathologie Humaine, Lyon, France
    2. CIRAD-INRA, UMR CMAEE, Guadeloupe, France
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  • Roman Rouzier,

    1. Department of Obstetrics and Gynecology, Hopital Tenon, Assistance Publique des Hopitaux de Paris, CancerEst, Universite Pierre et Marie Curie (UPMC), Paris, France
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  • Edgardo D. Carosella,

    1. CEA, IMETI, Service de Recherches en Hemato-Immunologie, Paris, France
    2. Univ Paris Diderot, Sorbonne Paris Cité, IUH, Hopital Saint-Louis, UMR_E, Paris, France
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  • Nathalie Rouas-Freiss,

    1. CEA, IMETI, Service de Recherches en Hemato-Immunologie, Paris, France
    2. Univ Paris Diderot, Sorbonne Paris Cité, IUH, Hopital Saint-Louis, UMR_E, Paris, France
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  • Catherine Menier

    Corresponding author
    1. Univ Paris Diderot, Sorbonne Paris Cité, IUH, Hopital Saint-Louis, UMR_E, Paris, France
    • CEA, IMETI, Service de Recherches en Hemato-Immunologie, Paris, France
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Dr. Catherine Menier, CEA, IMETI, Service de Recherches en Hemato-Immunologie Hopital Saint-Louis, Institut Universitaire d'Hematologie, 1, Avenue Claude Vellefaux, 75010 Paris, France Fax: +33-1-57276780 e-mail:catherine.menier@cea.fr

Abstract

Dimers of the nonclassical HLA-G class I molecule have recently been shown to be active structures that mediate inhibition of NK-cell cytotoxic activity through interaction with the immunoglobulin-like transcript (ILT)-2 inhibitory receptor. However, this has only been proven in trophoblasts and HLA-G transfectants. Here, we document for the first time the existence of HLA-G dimers in cancer. Indeed, we identified both surface and soluble HLA-G dimers in tumor cells and malignant ascites respectively. Interestingly, factors from the tumor microenvironment, such as interferons, enhanced the formation of HLA-G dimers and increased the protection of tumors from NK cell-mediated lysis. These data emphasize the impact of HLA-G conformation on its efficiency at inhibiting the antitumor response and thus favoring tumor progression. In view of these results, the effect of the tumor microenvironment on upregulation of HLA-G function deserves particular attention when designing cancer immunotherapy protocols.

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