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

Xuefeng Wang, Xin Zhao, Chao Feng, Aliyah Weinstein, Rui Xia, Wen Wen, Quansheng Lv, Shuting Zuo, Peijun Tang, Xi Yang, Xiaojuan Chen, Hongrui Wang, Shayang Zang, Lindsay Stollings, Timothy L. Denning, Jingting Jiang, Jie Fan, Guangbo Zhang, Xueguang Zhang, Yibei Zhu, Walter Storkus, & Binfeng Lu. Cancer cell (2015) 28, 296-306.

Speaker: Yi-Chun Chen (陳怡君)                                Time: 14:10~15:00, May. 25, 2016

Commentator: Dr. Ai-Li Shiau (蕭璦莉博士)             Place: Room 601

Abstract:

Many tumors induce adaptive immune responses, and the higher number of tumor-infiltrating type 1 lymphocytes, defined as interferon (IFN-γ) -producing lymphocytes, correlates with a better prognosis for cancer patients. (1) Cytokines play a pivotal role in regulating tumor immunogenicity and antitumor immunity. Interleukin 36γ (IL-36γ), member of the IL-1 family, is a candidate antitumor cytokine because of its role in promoting Th1 immune responses. (2) IL-36γ binds to the receptor complex, composed of the IL-36 receptor (IL-36R, also known as IL-1Rrp2 or IL-1RL2) and IL-1RAcP. (3) At moment, its function in other type 1 antitumor lymphocytes, such as CD8⁺ T cells, natural killer (NK) cells, and γδ T cells, is still poorly characterized. In this study, the authors demonstrated a role of IL-36γ in antitumor response and how does it effects. First, IL-36γ promotes IFN-γ production by CD8, NK, and γδ T cells. Second, tumor cells expressing IL-36γ have increased number of tumor-infiltrating lymphocytes (TILs) and exerted a strong antitumor activities. Third, tumoral expression of IL-36γ can serve as an effective tumor vaccination approach. Final, expression of IL-36γ correlates inversely with the progression of human cancer. Taken together, this study establishes an antitumor role of IL-36γ that has important implications for tumor immune therapy.

References:

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