IL-10 Elicits IFN gamma-Dependent Tumor Immune Surveillance
Menée sur des modèles murins, cette étude montre qu'un traitement à l'interleukine 10 pégylée permet d'activer la surveillance immunitaire des tumeurs et de réduire la croissance tumorale
Tumor immune surveillance and cancer immunotherapies are thought to depend on the intratumoral infiltration of activated CD8+ T cells. Intratumoral CD8+ T cells are rare and lack activity. IL-10 is thought to contribute to the underlying immune suppressive microenvironment. Defying those expectations we demonstrate that IL-10 induces several essential mechanisms for effective antitumor immune surveillance: infiltration and activation of intratumoral tumor-specific cytotoxic CD8+ T cells, expression of the Th1 cytokine interferon-³ (IFN³) and granzymes in CD8+ T cells, and intratumoral antigen presentation molecules. Consequently, tumor immune surveillance is weakened in mice deficient for IL-10 whereas transgenic overexpression of IL-10 protects mice from carcinogenesis. Treatment with pegylated IL-10 restores tumor-specific intratumoral CD8+ T cell function and controls tumor growth. º PEG-IL-10 induces the CD8+ T cell-mediated regression of large tumor masses º IL-10 directly induces cytotoxic enzymes and IFN³ in CD8+ T cells º IL-10 induces antigen presentation indirectly through CD8+ T cell-derived IFN³ º In human tumors, IL-10 expression correlates with granzymes, IFN³, and MHC
Cancer cell , résumé, 2010