Intratumoral dendritic cell dynamics in responsive and nonresponsive syngeneic murine tumor models

Conventional dendritic cells (cDC) play a vital role in T-cell-mediated antitumor immunity by transporting and cross-presenting tumor antigens to CD8 T-cells in draining lymph nodes (dLN) and tumor tissue. DC maturation and antigen uptake takes place in the tumor, which can be heavily affected by the suppressive tumor microenvironment. Intratumoral DCs are a scarce population and their phenotypes and functions have not been fully understood. Here we thoroughly characterized cDC phenotypes and dynamics in a variety of commonly used syngeneic murine tumor models, both at baseline and following anti-PD-L1 (aPDL1) treatment to investigate the correlation and potential contribution of DCs to response. Surprisingly, we observed a lower density of intratumoral DCs in responsive tumor models when compared to nonresponsive ones and their abundance was further reduced by aPDL1 treatment in an IFNg-dependent manner. Their PDL1 expression levels, albeit lower than tumor macrophages, were positively correlated with response. These results demonstrate an inverse correlation between intratumoral DCs and aPDL1-mediated antitumor immunity across different syngeneic murine tumor models, and ongoing studies are exploring the fates of these intratumoral DCs with a focus on their causal relation with the efficacy of immunotherapy. Citation Format: Huizhong Xiong, Stephanie Mittman, Ryan Rodriguez, Marina Moskalenko, Patricia Pacheco Sanchez, Yagai Yang, Rafael Cubas. Intratumoral dendritic cell dynamics in responsive and nonresponsive syngeneic murine tumor models [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr A120.