| Project/Area Number |
18K08787
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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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| Review Section |
Basic Section 55040:Respiratory surgery-related
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
豊川 剛二 独立行政法人国立病院機構九州医療センター(臨床研究センター), その他部局等, 呼吸器外科医師 (30627261)
平井 文彦 九州大学, 医学研究院, 共同研究員 (70645407)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 悪性胸膜中皮腫 / 肺癌 / 免疫療法 / 腫瘍浸潤リンパ球 / IDO |
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| Outline of Final Research Achievements |
Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive effector. IDO1 was expressed in the specimen of lung adenocarcinoma as well as malignant pleural mesothelioma (MPM). IDO1 positivity was associated with malignant traits of these tumors and poor prognosis. IDO1 and PD-L1 proteins were co-expressed in both tumors, and co-expressing tumors exhibited significantly more malignant traits and were associated with poor prognosis. In a mouse model of MPM, IDO1 and PD-L1 were also co-expressed and these expressions were associated with the increase of regulatory immune cells in the tumor microenvironment. These results suggest that IDO1 and PD-L1 co-expression may define an aggressive form of thoracic malignancies and indicate that IDO1 and PD-L1 co-expression could be a predictive maker and both are therapeutic targets.
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| Academic Significance and Societal Importance of the Research Achievements |
肺癌や悪性胸膜中皮腫などの胸部悪性腫瘍は、近年の手術法の進歩、免疫療法を始めとした薬物療法の進化に関わらず、いまだに難治癌であり、新たな治療標的の同定が重要である。免疫抑制性酵素のIDO1は新たな治療標的因子として期待されており、今回の我々の研究は、肺腺癌、悪性胸膜中皮腫においてIDO1発現腫瘍の特徴、免疫チェックポイント分子および免疫抑制性腫瘍浸潤リンパ球との関連を明らかとし、新たな複合免疫療法を開発する基礎的なデータになるものと思われる。
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