IL-36γ Transforms the Tumor Microenvironment and Promotes Type 1 Lymphocyte-Mediated Antitumor Immune Responses

Cytokines play a pivotal role in regulating tumor immunogenicity and antitumor immunity. IL-36 gamma is important for the IL-23/IL-17-dominated inflammation and anti-BCG Th1 immune responses. However, the impact of IL-36 gamma on tumor immunity is unknown. Here we found that IL-36 gamma stimulated CD8(+) T cells, NK cells, and gamma delta T cells synergistically with TCR signaling and/or IL-12. Importantly, IL-36 gamma exerted profound antitumor effects in vivo and transformed the tumor microenvironment in favor of tumor eradication. Furthermore, IL-36 gamma strongly increased the efficacy of tumor vaccination. Moreover, IL-36 gamma expression inversely correlated with the progression of human melanoma and lung cancer. Our study establishes a role of IL-36 gamma in promoting antitumor immune responses and suggests its potential clinical translation into cancer immunotherapy.