| Project/Area Number |
26430165
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Tumor therapeutics
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| Research Institution | Kumamoto University |
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Principal Investigator |
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| 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)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| 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 / 抗腫瘍免疫 / 癌免疫療法 / CD4陽性T細胞 / 可溶性IL-6受容体 / Th1分化 |
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| 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.
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