2023 Fiscal Year Final Research Report
Elucidation of a Novel Mechanism Regulating PD-L1 Expression in Lung Cancer and Its Role in Immune Evasion
| Project/Area Number |
20K09179
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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 | Ehime University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
坂上 倫久 愛媛大学, 医学系研究科, 講師(特定教員) (20709266)
岡崎 幹生 岡山大学, 大学病院, 講師 (50467750)
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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Keywords | 肺がん / 癌免疫チェックポイント阻害剤 / PD-L1 / NEDD8 |
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| Outline of Final Research Achievements |
There is a positive correlation between the therapeutic effect of immune checkpoint inhibitors and the expression level of PD-L1 in lung cancer tissues. Unveiling the mechanism regulating PD-L1 expression in lung cancer cells is crucial for establishing effective therapeutic methods. In this study, we used MLN4924, a NEDD8 modification inhibitor, to identify PD-L1 transcription factors activated in a NEDD8 modification-dependent manner, which regulate PD-L1 expression. As a result, we found that MLN4924 enhances glycolysis in lung cancer cells and regulates PD-L1 expression through a novel signaling pathway distinct from the previously reported interferon-dependent PD-L1 expression enhancement cascade.
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| Free Research Field |
呼吸器外科学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究で得られた研究成果は、癌免疫チェックポイント阻害療法で最も重要な肺癌細胞におけるPD-L1の発現制御メカニズムの一端を明らかにしたものであり、今後の肺がん治療にとって重要なエビデンスとなる。PD-L1の発現量を自在に制御できる手法が開発できると、癌免疫チェックポイント阻害剤を用いた肺がん治療の効率向上が期待でき、今後の臨床研究に大きくつながるものと考えられる。
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