Ag-presenting CpG-activated pDCs prime Th17 cells that induce tumor regression

Plasmacytoid dendritic cells (pDCs) rapidly and massively produce type I interferon and other inflammatory cytokines in response to foreign nucleic acids, thereby indirectly influencing adaptive T cell responses. Moreover, pDCs present Ag to naïve T cells and directly regulate T cell differentiation. Depending on the immune environment, pDCs exhibit either tolerogenic or immunogenic properties. Here we show that CpG-activated pDCs promote efficient Th17 differentiation. Indeed, Th17 responses are defective in mice selectively lacking MHCII on pDCs upon antigenic challenge. Importantly, in those mice, the frequency of Th17 cells infiltrating solid tumors is impaired. As a result, the recruitment of infiltrating leukocytes in tumors, including tumor-specific CTLs, is altered and results in increased tumor growth. Importantly, following immunization with tumor Ag and CpG-B, MHCII-restricted Ag presentation by pDCs promotes the differentiation of anti-tumor Th17 cells that induce intratumor CTL recruitment, and subsequent regression of established tumors. Our results highlight a new role for Ag presenting activated pDCs in promoting the development of Th17 cells and impacting on anti-tumor immunity.