| Project/Area Number |
18K15928
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53030:Respiratory medicine-related
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| Research Institution | Kumamoto University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 腫瘍免疫 / 腸内細菌叢 / 免疫チェックポイント阻害剤 / 肺がん / T細胞 / dysbiosis / 免疫療法 / 肺癌 / 腸内細菌 / がん免疫 / 腫瘍免疫微小環境 / がん免疫療法 / PDー1 / 腫瘍抗原 / COVID-19 / SARS-CoV-2 / PD-1 / PD-L1 / 末梢血単核球細胞（PBMC） / T 細胞 |
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| Outline of Final Research Achievements |
The effectiveness of immune checkpoint inhibitors (ICIs) is limited, and the development of new therapeutic strategies is an urgent issue. In this study, we conducted research with the aim of developing a new cancer immunotherapy that combines ICI (tumor immune suppression release) and active immune promotion. We discovered that T cells expressing Drebrin, which is important for the formation of immune synapses between T cells and antigen-presenting cells, are exhausted T cells, and patients with an increased Drebrin-positive T cells infiltrated into tumor cell nests have a high risk of recurrence, suggesting a potential new predictive factor for cancer treatment efficacy. We also conducted research focusing on the possibility that intestinal bacteria promote active immunity, and found that when CBM588 was administered as an intestinal regulation agent, the dysbiosis of intestinal flora was improved and the response to ICI and survival in patients with lung cancer were improved.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究成果は、T細胞におけるdrebrin発現が新たな疲弊T細胞マーカーであることを見出したことにより腫瘍免疫学の発展に貢献する。また、肺がんの術後再発予測に貢献すると同時に周術期に用いられるようになった免疫チェックポイント阻害剤（ICI）の新たな効果予測因子同定の一助となりうる成果である。また、腸内細菌叢を標的とした治療により能動免疫を活性化する戦略とICIを組み合わせることにより、新たたな併用療法の可能性を示した。本研究成果は、腸内細菌叢を標的とし進行肺がん治療の開発への論理的根拠を築き、ICI単独では恩恵が得られない患者やICIに薬剤耐性を示す患者への新たな治療法の開発に貢献する。
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