• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Identification of self-derived molecules that orchestrate tumor microenvironment

Research Project

Project/Area Number 18K15179
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 49070:Immunology-related
Research InstitutionThe University of Tokyo

Principal Investigator

Hangai Sho  東京大学, 先端科学技術研究センター, 特任助教 (50785350)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsがん微小環境 / DAMPs / 骨髄由来免疫抑制細胞 / MDSCs / MDSC
Outline of Final Research Achievements

We have identified a mechanism by which a novel damage-associated molecular pattern (DAMP), identified by the applicant, regulates the tumor microenvironment (TME) and promotes cancer growth. Through a series of analyses, we found that the novel DAMP induces CXCL1 chemokines via the innate immune receptor Toll-like receptor 2 (TLR2). Furthermore, we found that CXCL1 in turn recruits myeloid-derived suppressor cells, which have potent immunosuppressive activity, to the TME and suppresses the anti-tumor immune response thereby promoting tumor growth.

Academic Significance and Societal Importance of the Research Achievements

本研究によりがん細胞より放出される新規DAMPが、TMEを制御しがん増殖を促進するメカニズムの概要が明らかになった。申請者は新規DAMPが、CXCL1/2を誘導し、MDSCを誘導することで抗腫瘍免疫応答を抑制し、がん増殖を促進することを明らかにした。また、ヒト検体の解析により、ヒトにおいても新規DAMPがTME制御によりがん進展を促進している可能性が示唆された。本研究は近年進展が著しい、自己由来分子によるTME制御メカニズムに新たな視点を提供したものと考えられる。今後、新規DAMP中和抗体の抗腫瘍効果の検討を進めることで、新規DAMPの治療標的としての役割が明らかになることが期待される

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (10 results)

All 2021 2020 2019 2018 Other

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (2 results) (of which Int'l Joint Research: 1 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] HMGB1-mediated chromatin remodeling attenuates Il24 gene expression for the protection from allergic contact dermatitis2021

    • Author(s)
      Senda N, Yanai H, Hibino S, Li L, Mizushima Y, Miyagaki T, Saeki M, Kishi Y, Hangai S, Nishio J, Sugaya M, Taniguchi T, Sato S
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 118 Issue: 1

    • DOI

      10.1073/pnas.2022343118

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Signal transducing innate receptors in tumor immunity2021

    • Author(s)
      Hangai Sho、Kimura Yoshitaka、Taniguchi Tadatsugu、Yanai Hideyuki
    • Journal Title

      Cancer Science

      Volume: - Issue: 7 Pages: 2578-2591

    • DOI

      10.1111/cas.14848

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The impact of damage-associated molecules released from canine tumor cells on gene expression in macrophages2021

    • Author(s)
      Eto Shotaro、Yanai Hideyuki、Hangai Sho、Kato Daiki、Nishimura Ryohei、Nakagawa Takayuki
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 8525-8525

    • DOI

      10.1038/s41598-021-87979-1

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of U11snRNA as an endogenous agonist of TLR7-mediated immune pathogenesis.2019

    • Author(s)
      Negishi H, Endo N, Nakajima Y, Nishiyama T, Tabunoki Y, Nishio J, Koshiba R, Matsuda A, Matsuki K, Okamura T, Negishi-Koga T, Ichinohe T, Takemura S, Ishiwata H, Iemura SI, Natsume T, Abe T, Kiyonari H, Doi T, Hangai S, Yanai H, Fujio K, Yamamoto K, Taniguchi T.
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 116 Issue: 47 Pages: 23653-23661

    • DOI

      10.1073/pnas.1915326116

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Revisiting the role of IRF3 in inflammation and immunity by conditional and specifically targeted gene ablation in mice2018

    • Author(s)
      Yanai Hideyuki、Chiba Shiho、Hangai Sho、Kometani Kohei、Inoue Asuka、Kimura Yoshitaka、Abe Takaya、Kiyonari Hiroshi、Nishio Junko、Taguchi-Atarashi Naoko、Mizushima Yu、Negishi Hideo、Grosschedl Rudolf、Taniguchi Tadatsugu
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 115 Issue: 20 Pages: 5253-5258

    • DOI

      10.1073/pnas.1803936115

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Novel chemical compound SINCRO with dual function in STING-type I interferon and tumor cell death pathways2018

    • Author(s)
      Kimura Yoshitaka、Negishi Hideo、Matsuda Atsushi、Endo Nobuyasu、Hangai Sho、Inoue Asuka、Nishio Junko、Taniguchi Tadatsugu、Yanai Hideyuki
    • Journal Title

      Cancer Science

      Volume: 109 Issue: 9 Pages: 2687-2696

    • DOI

      10.1111/cas.13726

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Role HMGB1 in regulation of stem cell homeostasis2019

    • Author(s)
      半谷 匠
    • Organizer
      第48回 日本免疫学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] PROSTAGLANDIN E2 IS AN INHIBITORY DAMAGE ASSOCIATED MOLECULAR PATTERN WHICH CRITICALLY REGULATES STERILE INFLAMMATION-RELATED DISEASES INDUCED BY DEAD CELLS2018

    • Author(s)
      Sho Hangai, Hideyuki Yanai, Tadatsugu Taniguchi
    • Organizer
      Cytokines 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Remarks] 自然免疫応答を活性化する新たな自己RNAを同定

    • URL

      https://www.rcast.u-tokyo.ac.jp/ja/news/release/20191105.html

    • Related Report
      2019 Research-status Report
  • [Patent(Industrial Property Rights)] がん免疫微小環境の調節物質およびそれによる予防・診断・治療的利用2020

    • Inventor(s)
      谷口維紹、半谷匠、柳井秀元
    • Industrial Property Rights Holder
      谷口維紹、半谷匠、柳井秀元
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-147222
    • Filing Date
      2020
    • Related Report
      2020 Annual Research Report

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi