Interferon-γ reverses the immunosuppressive and protumoral properties and prevents the generation of human tumor-associated macrophages - Centre de recherche en cancérologie Nantes-Angers Unité Mixte de Recherche 892 Inserm - 6299 CNRS Accéder directement au contenu
Article Dans Une Revue International Journal of Cancer Année : 2009

Interferon-γ reverses the immunosuppressive and protumoral properties and prevents the generation of human tumor-associated macrophages

Résumé

Tumor-associated macrophages (TAM) are M2d-polarized cells (IL-10 high , IL-12 low , ILT3 high , CD86 low) that accumulate in tumor microenvironment. TAM inhibit antitumor T lymphocyte generation and function, contribute to tumor tolerance and are trophic for tumors. In this study, we investigated whether some immunological factors may reverse TAM immunosuppressive properties. Among 32 cytokines, we have identified IFNc on its ability to switch immunosuppressive TAM into immunostimulatory cells. Upon IFNc exposure, TAM purified from ovarian cancer ascites recover a M1 phenotype (IL-10 low , IL-12 high), express high levels of CD86 and low levels of ILT3, enhance the proliferation of CD4 1 T lymphocytes and potentiate the cytotoxic properties of a MelanA-specific CD8 1 T cell clone. IFNc-treated TAM also secreted reduced levels of mediators promoting suppressive T cell accumulation (CCL18) and trophic for tumors (VEGF and MMP9). As TAM derive from the local differentiation of peripheral blood monocytes, we investigated whether IFNc may also affect TAM generation. In the presence of ovarian ascites, IFNc skewed monocyte differentiation from TAM-like cells to M1polarized immunostimulatory macrophages. Together, these data show that IFNc overcomes TAM-induced immunosuppression by preventing TAM generation and functions. These data highlight that IFNc used locally at the tumor site could potentiate the efficacy of antitumor immunotherapies based on the generation of effector T cells.

Domaines

Immunologie
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Dates et versions

inserm-03377765 , version 1 (14-10-2021)

Identifiants

Citer

Dorothée Duluc, Murielle Corvaisier, Simon J. Blanchard, Laurent Catala, Philippe Descamps, et al.. Interferon-γ reverses the immunosuppressive and protumoral properties and prevents the generation of human tumor-associated macrophages. International Journal of Cancer, 2009, 125 (2), pp.367 - 373. ⟨10.1002/ijc.24401⟩. ⟨inserm-03377765⟩
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