Project/Area Number |
19K09310
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 55040:Respiratory surgery-related
|
Research Institution | Fukushima Medical University |
Principal Investigator |
|
Project Period (FY) |
2019-04-01 – 2023-03-31
|
Project Status |
Completed (Fiscal Year 2022)
|
Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
Keywords | 肺癌 / 免疫療法 / T細胞療法 / 癌免疫 / 腫瘍抗原 / がん免疫 / 細胞治療 / Neo-antigen / 免疫細胞療法 |
Outline of Research at the Start |
腫瘍局所浸潤リンパ球(TIL)のなかで,腫瘍特異的T細胞 rich な subsetの候補としてのCD39+/CD8+T細胞に着目し,この細胞群とTumor mutation burden(TMB)の解析を併用し,より簡便にNeoantigen 特異的T細胞療法を行うための理論的根拠を確立し,臨床応用も視野に入れた検討を行う.
|
Outline of Final Research Achievements |
The aim of this study was to clarify the rationale for a novel cell-based cancer immunotherapy targeting specific T cells in the tumor microenvironment. We first analyzed the tumor microenvironment in detail and found that the presence of tertiary lymphoid-like structures (TLS) is associated with the prognosis of lung cancer patients and the efficacy of immunotherapy. On the other hand, we confirmed the frequency and behavior of CD8 T cells with specific T cell receptors at the tumor site, and confirmed the expansion of tumor-specific T cells to the periphery. These results provide important basic data for the practical application of tumor-specific T-cell therapy.
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Academic Significance and Societal Importance of the Research Achievements |
各種癌に対する免疫チェックポイント阻害薬(ICI)を用いた治療が開発され,一部の症例では劇的な効果を発揮する.しかしその効果は限定的であり効果予測因子の抽出とさらなる効果の向上が求められている.本研究によって,腫瘍微小環境におけるTLSの存在が肺癌患者の予後のみならずICI療法の効果予測因子になることを明らかにした点で意義が大きい.また微小環境のみならず末梢血における変化も確認しており,今後の応用が期待される.また,特定のTCRクローンの挙動を解明することで,今後新たな細胞療法の可能性に貢献する結果を得ることができた.
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