The detrimental effect of soluble IL-6 receptor on CD4 T cell-mediated anti-tumor immune responses

2016 Fiscal Year Final Research Report

• Project/Area Number: 26430165
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor therapeutics
• Research Institution: Kumamoto University
• Principal Investigator: Tsukamoto Hirotake (塚本博丈) 熊本大学, 大学院生命科学研究部(医), 助教 (10433020)
• Research Collaborator: Fujieda Koji 熊本大学, 生命科学研究部, リサーチアシスタント ; Ikeda Tokunori 熊本大学, 医学部付属病院, 病院職員 (00613530) ; Nakayama Hideki 熊本大学, 生命科学研究部, 教授 (70381001) ; Araki Kimi 熊本大学, 生命資源研究・支援センター, 教授 (90211705) ; Senju Satoru 熊本大学, 生命科学研究部, 准教授 (50274709) ; Nishimura Yasuharu 熊本大学, 生命科学研究部, 教授 (10156119)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 抗腫瘍免疫応答 / 炎症 / T細胞 / IL-6 / 免疫抑制 / がん免疫療法 / sIL-6R

Outline of Final Research Achievements

It is well known that pro-inflammatory cytokine IL-6 produced by tumor cells promotes their own survival, therefore is a poor prognostic factor in cancer patients. In terms of anti-tumor immune responses, Th1 differentiation of tumor-specific CD4 T cells is attenuated in tumor-bearing animals in an IL-6-dependent fashion. In this study, we investigated the immune-suppressive effects of IL-6 signaling by focusing on IL-6 trans-signaling mediated thorough a soluble form of IL-6 receptor (sIL-6R).
We found that accompanied by the systemic increase of sIL-6R in cancer patients, blunted activity of sIL-6R restored the Th1 responses, their helper activity toward CD8 T cells, and anti-tumor activity in tumor-bearing mice. Our findings suggest the implication of the increase in IL-6 signaling as an adverse event counteracting tumor-specific Th1 generation, and that sIL-6R is considered for a rational target to improve the effectiveness of T cell-mediated cancer immunotherapy.

Free Research Field

免疫学