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2020 年度 実績報告書

Regulation of oxidative metabolic product-mediated immune suppressive tumor microenvironment to improve the efficacy of immune checkpoint blockade therapy in cancers.

研究課題

研究課題/領域番号 19K16808
研究機関慶應義塾大学

研究代表者

Sayem MohammadAbu  慶應義塾大学, 医学部(信濃町), 特任助教 (80772920)

研究期間 (年度) 2019-04-01 – 2021-03-31
キーワードVAP-1 inhibitor / H2O2 / Immunosuppression / CTLs / ICBs
研究実績の概要

In this study, the role of VAP-1 in TME was investigated. Intraperitoneal administration of the VAP-1-specific inhibitor U-V296 inhibited murine tumor growth by enhancing IFN-γ-producing tumor antigen-specific CD8+ T cells. U-V296 exhibited significant synergistic anti-tumor effects with ICIs. In the TME of mice treated with U-V296, the expressions of genes associated with immunosuppression were significantly decreased. H2O2, which promoted the production of IL-4 by mouse Th2 and inhibited IFN-γ by mouse Th1 and human tumor-infiltrating lymphocytes, was decreased. These results indicated that VAP-1 is involved in the immunosuppressive TMEs through H2O2-associated Th2/M2 conditions and may be an attractive target for the development of combination cancer immunotherapy with ICIs.

  • 研究成果

    (1件)

すべて 2021

すべて 雑誌論文 (1件) (うち査読あり 1件、 オープンアクセス 1件)

  • [雑誌論文] Inhibition of vascular adhesion protein-1 enhances the anti-tumor effects of immune checkpoint inhibitors2021

    • 著者名/発表者名
      Tomonari Kinoshita, Mohammad Abu Sayem, Tomonori Yaguchi, Budiman Kharma, Kenji Morii, Daiki Kato, Shigeki Ohta, Yukihiko Mashima, Hisao Asamura, Yutaka Kawakami
    • 雑誌名

      Cancer Science

      巻: 112(4) ページ: 1390-1401

    • DOI

      10.1111/cas.14812

    • 査読あり / オープンアクセス

URL: 

公開日: 2021-12-27  

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