Interleukin-1α mediates innate and acquired resistance to immunotherapy in melanoma

In a syngeneic mouse model of melanoma, we found that tumor size was inversely correlated with response to immunotherapy. Large tumors had higher levels of IL-1α, Th2 cytokines, granulocytic myeloid-derived suppressor cells (GMDSCs), and regulatory T cells but lower levels of IL-12, Th1 cytokines, and activated CD4+ and CD8+ T cells. Blocking IL-1 signaling decreased GMDSCs and their associated PD-L1 expression in the tumor microenvironment, and enhanced tumor-specific immunity. C57BL/6 mice were inoculated with the syngeneic B16 melanoma cell line, and after 8 days developed tumors that were either small (10-20 mm2) or large (70-80 mm2). Gene expression analysis was used to compared small vs. large tumors.