| Project/Area Number |
17K16420
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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 |
Radiation science
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| Research Institution | Gunma University |
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Principal Investigator |
Sato Hiro 群馬大学, 重粒子線医学推進機構, 助教 (90750571)
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 放射線治療 / 免疫チェックポイント / DNA二本鎖切断 / 放射線腫瘍免疫 / 炭素イオン線照射 / X線照射 / 放射線 / 腫瘍免疫 |
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| Outline of Final Research Achievements |
DNA damage signal-dependent PD-L1 induction was observed after X-ray irradiation and chemotherapeutic agent treatment. In addition, DNA damage signal-dependent PD-L1 expression was enhanced via Chk1 activation in Ku80 or BRCA2 knockdown cancer cells. These data revealed that Chk1 activation is important for PD-L1 induction after DNA damage. Furthermore, the STAT1 / 3-IRF1 pathway is also involved in the induction of PD-L1 expression by DNA double strand breaks.
Taken together, the mechanism by which the DNA damage response is involved in the regulation of PD-L1 expression in tumor cells was elucidated.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究にて、腫瘍細胞のPD-L1発現に影響するDNA修復関連遺伝子を明らかにしたことで、患者一人ひとりのDNA修復関連遺伝子の変異状況の評価により、放射線治療や化学療法と抗PD-1/PD-L1抗体を併用した場合の効果予測が可能となり、患者の個人レベルでの治療効果の改善に貢献できると考えている。さらに、抗PD-1抗体の医療費は高額であることから、放射線治療と抗PD-1抗体治療併用の症例毎の有効性の予測は、医療費における経済的メリットにも繋がると考えられる。
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