IL-36γ promotes antitumor immune responses (TUM10P.1028)

Abstract Introduction of an appropriate inflammation to tumor should greatly increase tumor immunogenicity and thereby help breaking immune tolerance to tumor antigens and increase response rates of immunotherapy. Cytokines play a pivotal role in regulating tumor immunogenicity and antitumor immunity. IL-36γ is important for the IL-23/IL-17-dominated autoimmune diseases as well as anti-BCG Th1 immune responses. However, the impact of IL-36γ on tumor immunity is unknown. Here, we found IL-36γ stimulated IFN-γ production by CD8 T cells synergistically with TCR signaling and/or IL-12. Importantly, IL-36γ exerted profound antitumor effects in vivo and transformed the tumor microenvironment in favor of tumor eradication. Furthermore, IL-36γ strongly increased the efficacy of tumor vaccination. Our work also showed that IL-36γ expression in human cancers inversely correlated with cancer progression. Our study establishes a novel role of IL-36γ in promoting antitumor immune responses and suggests its potential clinical translation in cancer immunotherapy.