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キラーT細胞のエネルギー代謝機構の解析とPD-1阻害がん免疫治療の効果予測

Research Project

Project/Area Number 18J15051
Research Category

Grant-in-Aid for JSPS Fellows

Allocation TypeSingle-year Grants
Section国内
Research Field Immunology
Research InstitutionKyoto University

Principal Investigator

Kumar Alok  京都大学, 医学研究科, 特別研究員(DC2)

Project Period (FY) 2018-04-25 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2019: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2018: ¥1,000,000 (Direct Cost: ¥1,000,000)
KeywordsPD-1 / Immunosupression / PGC-1alpha / Biomarker / Mitochondrial activation / biomarker / cancer immunotherapy
Outline of Annual Research Achievements

We classified unresponsiveness reasons into i). unresponsvieness because of local reasons ii). unresponsiveness because of having systemic immunosuppressive property (SIP). In addition, we found immune response after PD-1 blockade is associated with mitochondrial activation. Based on this result, we concluded that mitochondrial activation could be biomarker to identify responder and nonresponders. Further, we found SIP-positive tumors release non-proteinaceous small molecule that inhibit mitochondrial activation and proliferation of T cells. Bezafibrate when used alongwith culture superntant cancels the suppressive effect of supernatnat. Bezafibrate treatment alongwith PD-1 blockade enhances the survival of host bearing SIP-positive tumor compared to PD-1 blockade alone.

Research Progress Status

令和元年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和元年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (7 results)

All 2020 2019 2018

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (4 results)

  • [Journal Article] Tumors attenuating the mitochondrial activity in T cells escape from PD-1 blockade therapy2020

    • Author(s)
      Kumar A, Chamoto K, Chowdhury PS, Honjo T
    • Journal Title

      eLife

      Volume: 9 Pages: 1-21

    • DOI

      10.7554/elife.52330

    • NAID

      120006936324

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Synergistically Triggers Reactive Oxygen Species and DNA Damage and Inhibits Salmonella enterica subsp. Enterica Serovar Typhi and Vibrio fluvialis2019

    • Author(s)
      Ghosh, T., Srivastava, S. K. Gaurav, A., Kumar, A., Kumar, P., Yadav, A. S., Pathania,, R., Navani, N. K.
    • Journal Title

      Applied and Environmental Microbiology

      Volume: 85 (4) Issue: 4

    • DOI

      10.1128/aem.02487-18

    • Related Report
      2018 Annual Research Report
  • [Journal Article] PPAR-Induced Fatty Acid Oxidation in T Cells Increases the Number of Tumor-Reactive CD8+ T Cells and Facilitates Anti–PD-1 Therapy2018

    • Author(s)
      Chowdhury, P. S., Chamoto, K., Kumar. A., Honjo, T
    • Journal Title

      Cancer Immunology Research

      Volume: 6 Pages: 1375-1387

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] Inhibition of mitochondria by tumor-derived small molecule leads to systemic unresponsiveness to PD-1 blockade therapy2019

    • Author(s)
      Alok Kumar, Kenji Chamoto, Tasuku Honjo
    • Organizer
      78th Annual Meeting of Japanese Cancer Association (JCA)
    • Related Report
      2019 Annual Research Report
  • [Presentation] Bezafibrate enhances PD-1 blockade efficacy by activating mitochondrial biogenesis and effector function of CTLs2018

    • Author(s)
      Kumar, A.
    • Organizer
      The 77th Annual Meeting of Japanese Cancer Association
    • Related Report
      2018 Annual Research Report
  • [Presentation] Mechanistic analysis of unresponsiveness to the PD-1 blockade therapy2018

    • Author(s)
      Kumar, A.
    • Organizer
      Immunocon 2018 (The 45th Annual conference of the Indian Immunology Society, New Delhi)
    • Related Report
      2018 Annual Research Report
  • [Presentation] Mechanistic analysis of unresponsiveness to the PD-1 blockade therapy2018

    • Author(s)
      Kumar, A.
    • Organizer
      The 9th Annual ISAJ Symposium (by Indian Scientists Association in Japan)
    • Related Report
      2018 Annual Research Report

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Published: 2018-05-01   Modified: 2024-03-26  

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