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Published on: January 17, 2025
IL-36γ Transforms the Tumor Microenvironment and Promotes Type 1 Lymphocyte-Mediated Antitumor Immune Responses
Xuefeng Wang1, Xin Zhao2, Chao Feng3
1Department of Immunology, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15261, USA; Department of Biochemistry and Molecular Biology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215123, China; Department of Immunology, Institute of Medical Biotechnology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215123, China.
Abstract:
Cytokines play a pivotal role in regulating tumor immunogenicity and antitumor immunity. IL-36γ is important for the IL-23/IL-17-dominated inflammation and anti-BCG Th1 immune responses. However, the impact of IL-36γ on tumor immunity is unknown. Here we found that IL-36γ stimulated CD8(+) T cells, NK cells, and γδ 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. Moreover, IL-36γ expression inversely correlated with the progression of human melanoma and lung cancer. Our study establishes a role of IL-36γ in promoting antitumor immune responses and suggests its potential clinical translation into cancer immunotherapy.
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