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In vivo major histocompatibility complex class I (MHCI) expression on MHCI^low tumor cells is regulated by γδ T and NK cells during the early steps of tumor growth

Joëlle Riond^1*, Stéphane Rodriguez^1*, Marie-Laure Nicolau¹, Talal al Saati² and Jean Edouard Gairin¹

¹Institut des Sciences et Technologies du Médicament de Toulouse (ISTMT), UMR2587, CNRS-Pierre Fabre, Toulouse, France

²Plateau technique d'histopathologie expérimentale de l'IFR150/Génopôle Toulouse-Midi Pyrénées, Toulouse, France

Abstract

Cell surface expression of MHC class I molecules by tumor cells is determinant in the interplay between tumor cells and the immune system. Nevertheless, the mechanisms which regulate MHCI expression on tumor cells are not clear. We previously showed that immune innate cells from the spleen can regulate MHCI expression on MHCI^low tumor cells. Here, using the murine model of B16 melanoma, we demonstrate that the MHCI status of tumor cells in vivo is regulated by the microenvironment. In subcutaneous grafts, induction of MHCI molecules on tumor cells is concomitant to the recruitment of lymphocytes and relies on an IFNγ-mediated mechanism. γδ T and NK cells are essential to this regulation. A small proportion of tumor-infiltrating NK cells and γδ T cells were found to produce IFNγ, suggesting a possible direct participation to the MHCI increase on the tumor cells upon tumor cell recognition. Depletion of γδ T cells increases the tumor growth rate, confirming their anti-tumoral role in our model. Taken together, our results demonstrate that in vivo, NK and γδ T cells play a dual role during the early growth of MHCI^low tumor cells. In addition to controlling the growth of tumor cells, they contribute to modifying the immunogenic profile of residual tumor cells.