CD83 via CCR7+DC limits intratumoral CD8 responses and promotes tumor growth 2510

Abstract Description CCR7+dendritic cells (DC) are associated with favorable responses to immune checkpoint blockade. They have been found in intratumoral niches in proximity of CD4+ and CD8+ T cells. How CCR7+DC control intratumoral T cell infiltration, restrain intratumoral responses, and influence cancer outcomes is not fully understood. Here we show that, by limiting the expression of activation marker CD83 on CCR7+DC, we could increase the intratumoral amount of CD8 T cells and control cancer in mice. Reduction of membrane-bound CD83 determines a pro-inflammatory CCR7+DC state that correlates with the expansion of intermediate effector-like CD8 and tumor control. Additionally, CD83 levels on CCR7+DC negatively correlate with intratumoral CD8 T cell infiltration in distinct human cancers. These observations reveal that CD83 on CCR7+DC is a cellular and molecular tumor checkpoint that limits CD8 T cell immune-responses and has the potential to be exploited in cancer treatment. Funding Sources Cancer Prevention and Research Institute of Texas (CPRIT; RR210017) Robert J. Kleberg, Jr. and Helen C. Foundation Melanoma SPORE Developmental Research Program (DRP; P50CA221703) American Association of Immunologists (AAI) Intersect Fellowship (AWD00007355) Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)