| Project/Area Number |
16K10415
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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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| Research Field |
Radiation science
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| Research Institution | Aichi Cancer Center Research Institute (2017-2019)
Foundation for Biomedical Research and Innovation (2016) |
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Principal Investigator |
Masago Katsuhiro 愛知県がんセンター(研究所), がん病態生理学分野, 研究員 (80338160)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 次世代シーケンサー / 放射線照射 / 非小細胞肺癌 / 腫瘍遺伝子変異量 / PD-L1 / 免疫チェックポイント阻害剤 / RNAシーケンス / 薬剤耐性 / 放射線治療 / PDL1 / トランスクリプトーム解析 / 免疫染色 |
|---|
| Outline of Final Research Achievements |
In the treatment of advanced non-small cell lung cancer, inhibition of the PD1-PD-L1 axis has become one of the novel treatment options, but the mechanism of activation of this pathway in tumorigenesis remains unclear. Therefore, in this study, we conducted a genetic analysis and gene expression analysis using pre-irradiation and post-irradiation tumor specimens in radical surgery cases where radiation therapy was performed as preoperative treatment, thereby determining the factors involved in this pathway. After radiotherapy, PD-L1 expression decreased by IHC and deletion mutations and single nucleotide mutations increased by genomic analysis. These results suggest that the genetic analysis of residual tumor subclones affected by preoperative treatment may also have important significance at the time of recurrence.
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| Academic Significance and Societal Importance of the Research Achievements |
非小細胞肺癌の治療において、放射線治療は根治的及び対症療法的にも多く用いられる。しかし、同治療が腫瘍細胞に与える影響に関しては不明な点が多いとされていた。今回の結果から、放射線照射によるPD-L1の低下によって内因性の抗腫瘍免疫の増加が治療効果に寄与していることが推定された。また、放射線照射による腫瘍細胞遺伝子の遺伝子変異の増加によって、再発時の免疫チェックポイント阻害剤の潜在的な効果も予想される結果であった。
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