| Project/Area Number |
17K16045
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Osaka University |
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Principal Investigator |
Koyama Shohei 大阪大学, 医学系研究科, 助教 (80767559)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
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| Keywords | がん免疫 / 好中球 / 抗PD-1抗体 / 肺がん / 非小細胞肺癌 / 活性化好中球 / 腫瘍浸潤T細胞 / 免疫療法耐性化 |
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| Outline of Final Research Achievements |
We investigated the tumor microenvironment in mouse lung cancer, and found that tumor cells recruited neutrophils that suppressed anti-tumor CD8 T cell function as a result of arginine depletion by arginase. Based on this finding, we treated the tumors with an arginase inhibitor. The lung tumor volume was significantly lower in the treated group than in the untreated group. We confirmed that an increased number of neutrophils in the peripheral blood was significantly correlated with a reduced response rate to anti-PD-1 antibody treatment. Therefore, targeting immune-suppressive neutrophils can be a vital option for lung cancer treatment with immune checkpoint inhibitors such as anti-PD-1 antibodies.
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| Academic Significance and Societal Importance of the Research Achievements |
抗PD-1抗体に代表されるがん免疫療法は、肺がんに限らず、標準的な治療法の一つとして、様々な固形腫瘍に対して適応が拡大されるに至った。しかしながら、単剤での効果が不十分であることから、併用治療を行うことでその効果を改善する取り組みが行われている。今回アルギナーゼを高発現する好中球が多いことが、治療抵抗性に関わる因子として判明し、その阻害剤がマウスモデルで有効であることを示した。今後もこの悪玉好中球を除去できるような治療法との併用が免疫療法の効果改善の糸口になる可能性が示唆される。
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