| Project/Area Number |
16K10499
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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 |
Digestive surgery
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| Research Institution | Okayama University |
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Principal Investigator |
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| Research Collaborator |
KATO takuya
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 癌関連線維芽細胞 / 腫瘍内リンパ球 / インターロイキン / 食道癌 / 腫瘍内浸潤リンパ球 / IL-6 / 腫瘍免疫抑制 / CAFs / esophageal cancer / TILs / tumor immunosuppression / interleukin 6 / がん微小環境 / がん関連線維芽細胞 / 腫瘍免疫 / 光線免疫療法 / 線維芽細胞 / 細胞標的治療 |
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| Outline of Final Research Achievements |
Cancer-associated fibroblasts (CAFs) have been considered to have a central role for tumor progression in tumor microenvironment. We identified that intra-tumoral CD8+ and FoxP3+ tumor-infiltrating lymphocytes (TILs) are independent prognostic factors in esophageal cancer tissue of clinical samples. In addition, CAFs had a significant correlation of those TILs in intra-tumoral, but not peri-tumoral sites, so that CAFs regulated the infiltration of CD8+ and FoxP3+ TILs into intra-tumor tissues. In vitro, CAFs activated by cancer cells secreted high levels of Interleukin 6 (IL-6). In vivo, CAFs accelerated tumor growth obviously in immune-competent mice, along with phenotypic change in T cell populations, decreased CD8+ and increased FoxP3+ TILs. Moreover, the accelerated tumor growth in CAFs co-cultures was significantly reduced by IL-6 blockade, demonstrating that immunosuppressive TILs population was improved.
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| Academic Significance and Societal Importance of the Research Achievements |
以上の結果は，腫瘍においてCAFsがリンパ球の浸潤をIL-6を用いて制御していることの解明に繋がった．IL-6は元来炎症性サイトカインであり腫瘍に対する影響はあまり報告がない．我々の発見した知見より，現在抗リウマチ薬として市販されている抗IL-6抗体やその他のIL-6阻害剤が癌の治療、すなわち腫瘍内のリンパ球の組成を改善し，腫瘍制御につながる可能性を示している．いわゆるドラッグリポジショニングの一つの可能性を示し医療経済的にも非常に有意義な研究結果である．
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