2023 Fiscal Year Final Research Report
Elucidation of immune checkpoint inhibitor resistance mechanism in lung cancer
| Project/Area Number |
19K09294
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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 | Saitama Medical University (2022-2023)
National Hospital Organization Saitama National Hospital (2019-2021) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
田中 文啓 産業医科大学, 医学部, 教授 (10283673)
米田 和恵 産業医科大学, 医学部, 講師 (80724806)
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| Project Period (FY) |
2019-04-01 – 2024-03-31
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| Keywords | 肺癌 / 癌免疫 / 免疫チェックポイント阻害剤 / 手術 / CTL / 細胞性免疫 / 免疫療法 / T細胞 |
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| Outline of Final Research Achievements |
We prospectively analyzed the relationship between immune-related molecule expression in peripheral blood mononuclear cells (PBMCs) and lung cancer tissues and the efficacy of Immune checkpoint inhibitor (ICI).Twenty-one patients with advanced non-small cell lung cancer who received ICI monotherapy were included. Changes in the expression of immune-related molecules in PBMCs before and after ICI administration were analyzed by flow cytometry. Immune-related molecule expression in cancer cells and tumor-infiltrating immune cells in lung cancer tissues was confirmed by immunostaining. The outcomes were CR/PR/SD/PD:1/7/10/3. In multivariate analysis of progression-free survival (PFS),the changes of CD103+ CD39+ CD8+ cells in PBMC after treatment was an independent prognostic factor. The changes in CD103+ CD39 + CD8 + cells after treatment may be a biomarker predicting the efficacy of ICIs.
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| Free Research Field |
呼吸器外科
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| Academic Significance and Societal Importance of the Research Achievements |
免疫チェックポイント阻害剤(ICI) 単剤投与肺癌症例の肺癌組織や末梢血リンパ球を解析し、ICIの効果、耐性予測因子の検討を行なった。ICI投与前にCD103+リンパ球が腫瘍内に浸潤しているような症例は、ICIに反応し、末梢血中にCD103+ CD39+CD8+細胞が増え、臨床効果も高くなると考えられた。さらなる解析が必要であるが、CD103+ CD39+CD8+細胞をバイオマーカーとして用いることで、ICI治療の正しい患者選択やより効果的な治療法の確立が実現出来る可能性がある。より効果的で安全な免疫療法を実現するのみならず、高額な免疫療法を真の個別化治療に導くことで医療費削減も期待できる。
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