| Project/Area Number |
16H05309
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | The University of Tokushima |
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Principal Investigator |
NISHIOKA Yasuhiko 徳島大学, 大学院医歯薬学研究部(医学域), 教授 (70274199)
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| Co-Investigator(Kenkyū-buntansha) |
後東 久嗣 徳島大学, 大学院医歯薬学研究部(医学域), 准教授 (00437641)
西條 敦郎 徳島大学, 大学院医歯薬学研究部(医学域), 特任助教 (00467812)
荻野 広和 徳島大学, 大学院医歯薬学研究部(医学域), 助教 (20745294)
埴淵 昌毅 徳島大学, 大学院医歯薬学研究部(医学系), 准教授 (80335794)
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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 |
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2018: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2016: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
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| Keywords | 線維細胞 / 肺がん / 血管新生 / がん幹細胞 / 免疫チェックポイント / がん免疫 / 免疫チェックポイント分子 |
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| Outline of Final Research Achievements |
To overcome drug resistance and develop the innovative therapy, the analysis of function of fibrocytes, which were identified to mediate the resistance mechanism for anti-angiogenic agents, were performed in the present study. We found the increased number of fibrocytes in peripheral blood of patients with lung cancer who showed the clinical resistance to anti-angiogenic therapy. In addition, fibrocytes showed the ability to generate stem cell-like phenotype of lung cancer cells in in vitro experiments, indicating the notion that regulating the function of fibrocytes might be critical to inhibit the progression of lung cancer. Immunological analysis showed that fibrocytes had the effects to up- or down-regulate T cell-immunity in vitro. Intra-tumoral administration with fibrocytes, furthermnore, enhanced the anti-tumor activity mediated by anti-PD-1 or anti-PD-L1 antibodies. These results indicate that fibrocytes play an important role in tumor-immunity.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究結果から線維細胞は肺がん細胞に直接作用して肺がんの腫瘍としての性格を悪い方向（がん幹細胞化）に調節していることが明らかになったことから、線維細胞を標的に治療法の開発研究を行う重要性が高まったと考えられる。血管新生阻害薬に耐性となった肺がん患者の末梢血には線維細胞が増加しており、耐性化のマーカーとなる可能性が示唆された。さらに、血管新生阻害薬と免疫チェックポイント阻害薬の併用効果に線維細胞の作用が関与している新たな可能性が示され、がん免疫療法のメカニズムの理解に繋がる重要な結果が得られたと考えられる。
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