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828 Combination of Flt3L and STING agonism sensitizes non-T cell-inflamed tumors to checkpoint blockade therapy

Background STING agonists have been pursued as a strategy to trigger innate immune activation within the tumor microen-vironment, which can lead to adaptive immunity and tumor regression in mice. However, clinically activity of STING agonists has been less impressive. We hypothesized that a low response rate clinically could be because most patients have non-T cell-inflamed (cold) tumors. We hypothesized that non-T cell-inflamed tumors may lack the required CD103 + dendritic cell (DC) subset for T cell priming, thus failing to make the bridge to adaptive immunity. To investigate this notion, we turned to a B-catenin-driven genetically engineered mouse melanoma model, which is non-inflamed and known to lack CD103 + DCs. We evaluated whether recruitment of CD103 + DCs via Flt3L might cooperate with a STING agonist to pro-mote tumor control, alone or in combination with checkpoint blockade antibodies. Methods We used the BRAF-activated, PTEN-deleted, B-cate-nin-stabilized (BPC) genetic melanoma model. Our laboratory previously showed that these tumors lack spontaneous CD103 + DC and T cell infiltration and have low expression of the chemokines known to recruit these cells, which closely resembles the biology of many non-T cell-inflamed human can-cers. To recruit and activate CD103 + DCs to these tumors, we injected intratumoral Flt3L alone, the STING agonist DMXAA alone, and both in combination.