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Enhancement of antitumor effect of IL-21 by improving cancer microenvironment

Research Project

Project/Area Number 17K07153
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Tumor biology
Research InstitutionIshinomaki Senshu University (2018-2019)
Yamagata University (2017)

Principal Investigator

Nara Hidetoshi  石巻専修大学, 理工学部, 准教授 (00375338)

Co-Investigator(Kenkyū-buntansha) 浅尾 裕信  山形大学, 医学部, 教授 (80250744)
武田 裕司  山形大学, 医学部, 准教授 (90302299)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsインターロイキン21 / 樹状細胞 / インターロイキン(IL-)21 / 免疫抑制 / IL-21 / マウス / マイクロアレイ解析 / 癌 / 免疫学
Outline of Final Research Achievements

Clinical trials of the treatment of malignant melanoma with IL-21 have been conducted, but to date no significant effect has been obtained. The present study was carried out on the basis that IL-21 may suppress activation of dendritic cells in tumor microenvironment and suppress activation of lymphocytes. Bone marrow-derived dendritic cells were newly found to be differentiated into five stages, and it was found that IL-21 arrests differentiation into mature dendritic cells at the third stage. We have comprehensively analyzed the patterns of genes expressed at this time, and are currently examining its function. In addition, in experiments using mice, it was possible to observe a decrease in immune response due to suppression of dendritic cells due to overexpression of IL-21.

Academic Significance and Societal Importance of the Research Achievements

がんを取り巻く微小な環境では、様々な要因により抗がん剤の影響が阻まれ、十分な効果を発揮できないことがある。IL-21は様々な白血球の活性化を誘導するので、抗腫瘍効果を期待されているが、際立った抗腫瘍効果は得られていない。IL-21は白血球の中で、抗原提示というリンパ球の活性化を担う樹状細胞の活性を抑制することが知られている。よって、その機構を解明することで、新たな治療薬の開発につながるのではないかと考えた。IL-21により、樹状細胞ではいくつかの遺伝子の発現パターンが異なることを見出し、これらを標的としうる可能性が示唆された。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (6 results)

All 2019 2018 2017 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (1 results) Remarks (1 results)

  • [Journal Article] IL-21 Enhances the Development of Colitis-Associated Colon Cancer: Possible Involvement of Activation-Induced Cytidine Deaminase Expression2019

    • Author(s)
      Araki Akemi、Jin Lianjin、Nara Hidetoshi、Takeda Yuji、Nemoto Nobuhito、Gazi Md Yeashin、Asao Hironobu
    • Journal Title

      The Journal of Immunology

      Volume: 202 Issue: 11 Pages: 3326-3333

    • DOI

      10.4049/jimmunol.1800550

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] nterleukin-21 attenuates FITC-induced contact hypersensitivity response via regulation of dendritic cell function2018

    • Author(s)
      Nara H, Komatsu M, TekedaY, Araki A, Akhter N, Asao H
    • Journal Title

      Journal of Investigative Dermatology

      Volume: 印刷中 Issue: 10 Pages: 2174-2184

    • DOI

      10.1016/j.jid.2018.03.1508

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Systemic neutrophil migration and rapid consumption of neutrophils in the spleen2018

    • Author(s)
      Takeda Yuji、Kato Tomoyuki、Nemoto Nobuhito、Araki Akemi、Gazi Mohammad Yeashin、Nara Hidetoshi、Asao Hironobu
    • Journal Title

      Data in Brief

      Volume: 20 Pages: 680-682

    • DOI

      10.1016/j.dib.2018.08.090

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Augmentation of the expression of the eotaxin receptor on duodenal neutrophils by IL-212018

    • Author(s)
      Takeda Yuji、Kato Tomoyuki、Nemoto Nobuhito、Araki Akemi、Gazi Mohammad Yeashin、Nara Hidetoshi、Asao Hironobu
    • Journal Title

      Cytokine

      Volume: 110 Pages: 194-203

    • DOI

      10.1016/j.cyto.2018.05.007

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] Interleukin21 arrests bone marrow derived dendritic cells PD-L1 high immunosuppressive state2017

    • Author(s)
      Nara H, TAKEDA Y, Md. GAZI Y, NEMOTO N, ARAKI A, ASAO H.
    • Organizer
      第46回 日本免疫学会学術集会
    • Related Report
      2017 Research-status Report
  • [Remarks] 山形大学医学部 免疫学講座 HP 業績欄

    • URL

      http://www.id.yamagata-u.ac.jp/Imm/gyouseki.html

    • Related Report
      2017 Research-status Report

URL: 

Published: 2017-04-28   Modified: 2021-02-19  

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