2022 Fiscal Year Final Research Report
Investigation of predictive factors for efficacy of immune heckpoint inhibitor in renal cell carcinoma
| Project/Area Number |
20K09574
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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 56030:Urology-related
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
溝上 敦 金沢大学, 医学系, 教授 (50248580)
泉 浩二 金沢大学, 附属病院, 講師 (80646787)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | 腎細胞癌 / 免疫チェックポイント / ケモカイン |
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| Outline of Final Research Achievements |
The combination of kahweol acetate and cafestol administration synergistically inhibited cell proliferation and migration by inducing apoptosis and inhibiting epithelial-mesenchymal transition. Mechanistic dissection revealed that kahweol acetate and cafestol inhibited AKT and ERK phosphorylation. Moreover, kahweol acetate and cafestol downregulated the expression of not only C-C chemokine receptors 2, 5, and 6 but also programmed death-ligand 1, indicating their effects on the tumor microenvironment. Although sera from patients with renal cell carcinoma were investigated to seek novel predictive factors for efficacy of immune heckpoint inhibitor in renal cell carcinoma, no factors were found this time.
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| Free Research Field |
泌尿器腫瘍学
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| Academic Significance and Societal Importance of the Research Achievements |
カーウェオールとカフェストールの直接的な抗腫瘍効果のメカニズムとして、ヒト腎細胞癌細胞に対するアポトーシスの誘導による増殖能の抑制と上皮間葉移行の阻害による遊走・転移能の抑制が明らかとなった。さらに、ケモカイン受容体やPD-L1の発現の抑制を介し、ケモカインシグナルの阻害、抗腫瘍免疫応答に作用し、間接的に癌微小環境にも影響しうることが示唆された。腫瘍免疫学的作用により間接的な抗腫瘍効果を発揮する可能性を有することを初めて示した基礎研究であり、腎細胞癌に対する新たな治療薬の開発に繋がる有益な研究であると考えられる。
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