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2022 Fiscal Year Final Research Report

Mechanism of predicting the effects of immune checkpoint inhibitors based on the diversity of cancer-associated fibroblasts

Research Project

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Project/Area Number 20H03528
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 50020:Tumor diagnostics and therapeutics-related
Research InstitutionNagoya University

Principal Investigator

Ando Yuichi  名古屋大学, 医学部附属病院, 教授 (10360083)

Co-Investigator(Kenkyū-buntansha) 榎本 篤  名古屋大学, 医学系研究科, 教授 (20432255)
Project Period (FY) 2020-04-01 – 2023-03-31
Keywordsがん関連線維芽細胞 / 腫瘍免疫応答 / 免疫チェックポイント阻害薬
Outline of Final Research Achievements

Meflin is a novel marker of cancer-associated fibroblasts (CAFs). In this study, we demonstrated that the prevalence of Meflin-positive CAFs correlates with favorable therapeutic effects to immune checkpoint inhibitors, using clinical specimens from patients with clear cell renal carcinoma and urothelial carcinoma. Furthermore, we clarified that the mechanism of tumor immunoregulation by this Meflin-positive CAF is the suppression of intratumor infiltration of CD11b-positive cells via complement C3 and its degradation product iC3b.

Free Research Field

がん薬物療法

Academic Significance and Societal Importance of the Research Achievements

がん関連線維芽細胞(CAF)の新規マーカーとしてMeflinを同定し、Meflin陽性CAFの存在量が免疫チェックポイント阻害薬の良好な治療効果に相関することを明らかにした。この分子メカニズムは、補体C3とその分解産物iC3bを介したCD11b陽性細胞の腫瘍内浸潤の抑制であることを明らかにした。局所間質産生補体C3は神経科学や発生学などで注目されているが、腫瘍微小環境におけるCAF由来補体C3に着目した研究は、我々の知る限り、本研究が最初である。

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Published: 2024-01-30  

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