2018 Fiscal Year Final Research Report
Molecular mechanism of PD-L1 upregulation in cancer cells after DNA double-strand break repair pathway following irradiation
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 |
Research Field |
Radiation science
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Research Institution | Gunma University |
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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Keywords | 放射線治療 / 免疫チェックポイント / DNA二本鎖切断 |
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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Free Research Field |
放射線生物学
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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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