In vivo major histocompatibility complex class I (MHCI) expression on MHCIlow tumor cells is regulated by gammadelta T and NK cells during the early steps of tumor growth.
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 IFNgamma-mediated mechanism. gammadelta T and NK cells are essential to this regulation. A small proportion of tumor-infiltrating NK cells and gammadelta T cells were found to produce IFNgamma, suggesting a possible direct participation to the MHCI increase on the tumor cells upon tumor cell recognition. Depletion of gammadelta 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 gammadelta 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.
Riond
Joëlle
J
Institut des Sciences et Technologies du Médicament de Toulouse, UMR2587, CNRS-Pierre Fabre, Toulouse, France. joelle.riond@istmt.cnrs.fr
Rodriguez
Stéphane
S
Nicolau
Marie-Laure
ML
al Saati
Talal
T
Gairin
Jean Edouard
JE
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008545:Melanoma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D015854:Up-Regulation
D015395:Histocompatibility Antigens Class I; D016692:Receptors, Antigen, T-Cell, gamma-delta; D007371:Interferon-gamma