IL-10 Elicits IFNγ-Dependent Tumor Immune Surveillance

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-γ (IFNγ) 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. [Display omitted] ► PEG-IL-10 induces the CD8 + T cell-mediated regression of large tumor masses ► IL-10 directly induces cytotoxic enzymes and IFNγ in CD8 + T cells ► IL-10 induces antigen presentation indirectly through CD8 + T cell-derived IFNγ ► In human tumors, IL-10 expression correlates with granzymes, IFNγ, and MHC