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2021 Fiscal Year Final Research Report

Enhance the efficacy of immune checkpoint inhibitors by targeting Meflin

Research Project

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Project/Area Number 20K22807
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0901:Oncology and related fields
Research InstitutionNagoya University

Principal Investigator

Miyai Yuki  名古屋大学, 医学部附属病院, 医員 (90883538)

Project Period (FY) 2020-09-11 – 2022-03-31
Keywordsがん / がん関連線維芽細胞 / 免疫チェックポイント阻害剤 / 効果予測 / 効果増強
Outline of Final Research Achievements

Most cancer-associated fibroblasts (CAF) shape the tumor microenvironment toward an immune-suppressive milieu and attenuate the efficacy of immune checkpoint inhibitors (ICI). On the other hand, we found that non-small cell lung cancer patients with a high number of Meflin expressing CAF subsets are associated with favorable outcomes for ICI monotherapy. Furthermore, we also reported that Meflin deficiency and CAF-specific Meflin overexpression resulted in defective and enhanced ICI responses in syngeneic tumors in mice, respectively. These findings suggest the presence of a CAF subset that promotes ICI efficacy, which tells us that future strategies targeting Meflin to augment the efficacy of ICI could be effective.

Free Research Field

腫瘍内科 腫瘍生物学 腫瘍免疫学

Academic Significance and Societal Importance of the Research Achievements

がん関連線維芽細胞CAFはこれまで、免疫抑制性の働きをすると考えられてきた。私たちの研究は、Meflin陽性CAFがこれまで報告されたCAFと異なり、免疫チェックポイント阻害剤の効果を増強するような働きがあることが判明した。この研究により、CAFの機能と不均質性についての理解がさらに深まったと考えられる。また、Meflinの発現を上げるような物質を投与することで、免疫チェックポイント阻害剤の効果の増強が期待できるかもしれないということでもあり、現在開発を進めている。

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Published: 2023-01-30  

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