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Elucidation of tumor immunoactivation mechanism by cancer microenvironment improving drug

Research Project

Project/Area Number 19K18594
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56030:Urology-related
Research InstitutionOsaka City University

Principal Investigator

Shunji Nishide  大阪市立大学, 大学院医学研究科, 研究員 (10803132)

Project Period (FY) 2019-04-01 – 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: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords腫瘍免疫 / 低酸素応答 / マクロファージ / PHD阻害薬 / 腫瘍関連マクロファージ / がん微小環境 / 腫瘍血管 / 腫瘍環境
Outline of Research at the Start

申請者らはこれまでに、PHD阻害薬を使用したがん微小環境の改善により、マクロファージの貪食活性化、腫瘍増殖の抑制を明らかにした。本研究ではPHD阻害薬により活性化したマクロファージが、腫瘍の増殖をどのように抑制するか詳細な機序を解明することを目的としている。

Outline of Final Research Achievements

Macrophages, which are abundant in tumors, promote tumor growth and metastasis in a hypoxic tumor environment, and are a major factor in deteriorating the prognosis of cancer patients. To. Applicants have previously found that PHD inhibitor improve the tumor environment and suppress tumor growth. In this study, based on the results of previous studies, we investigated whether the combined use of PD-1 antibody and CD47 antibody with PHD inhibitors could further suppress tumor growth.
Furthermore, by evaluating genetic changes in macrophages by administering PHD inhibitors, we are analyzing the mechanism of tumor growth suppression by macrophages activated by PHD inhibitors.

Academic Significance and Societal Importance of the Research Achievements

本研究により、腫瘍内で貪食が活性化した腫瘍関連マクロファージによって、組織障害性細胞(T細胞やNK細胞など)を活性化する詳細な機序が明らかにすれば、PHD阻害薬によるマクロファージの貪食活性を基盤とした新たな免疫療法が開拓できると考える。

Report

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

    (8 results)

All 2021 2020 2019

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

  • [Journal Article] Prolyl-hydroxylase inhibitors reconstitute tumor blood vessels in mice2020

    • Author(s)
      Nishide Shunji、Uchida Junji、Matsunaga Shinji、Tokudome Kentaro、Yamaguchi Takehiro、Kabei Kazuya、Moriya Taiki、Miura Katsuyuki、Nakatani Tatsuya、Tomita Shuhei
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 143 Issue: 2 Pages: 122-126

    • DOI

      10.1016/j.jphs.2020.02.010

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Controlling the Phenotype of Tumor-Infiltrating Macrophages via the PHD-HIF Axis Inhibits Tumor Growth in a Mouse Model2019

    • Author(s)
      Nishide Shunji、Matsunaga Shinji、Shiota Masayuki、Yamaguchi Takehiro、Kitajima Shojiro、Maekawa Yoichi、Takeda Norihiko、Tomura Michio、Uchida Junji、Miura Katsuyuki、Nakatani Tatsuya、Tomita Shuhei
    • Journal Title

      iScience

      Volume: 19 Pages: 940-954

    • DOI

      10.1016/j.isci.2019.08.033

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 新規腎性貧血治療薬4種類が腫瘍にもたらす影響の比較検討2021

    • Author(s)
      西出峻治
    • Organizer
      第54回日本臨床腎移植学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 経口腎性貧血治療薬による腫瘍免疫強化療法の開発2020

    • Author(s)
      西出峻治
    • Organizer
      第108回日本泌尿器科学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Alteration the phenotype of tumor-infiltrating macrophages via the PHD-HIF axis inhibits tumor growth in mice2020

    • Author(s)
      Shunji Nishide, Shinji Matsunaga, Takehiro Yamaguchi, Norihiko Takeda, Junji Uchida, Katsuyuki Miura, Tatsuya Nakatani and Shuhei Tomita
    • Organizer
      Hypoxia; KEYSTONE SYMPOSIA
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 新規経口腎性貧血治療薬による 腫瘍への影響2020

    • Author(s)
      西出 峻治、内田潤次、島田久生、香束昌宏、壁井和也、 岩井友明、熊田憲彦、長沼俊秀、武本佳昭、仲谷達也
    • Organizer
      第53回日本臨床腎移植学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 新規の経口腎性貧血治療薬Roxadustatによる 免疫系への影響2019

    • Author(s)
      西出 峻治、内田 潤次、松永 慎司、島田 久生、香束 昌宏 、壁井 和也、岩井 友明、長沼 俊秀、武本 佳昭、冨田 修平、仲谷 達也
    • Organizer
      第55回日本移植学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 腎性貧血治療薬Roxadustatを用いた 新たな腫瘍免疫療法の開拓2019

    • Author(s)
      西出 峻治、内田 潤次、松永 慎司、島田 久生、香束 昌宏、壁井 和也、 岩井 友明、長沼 俊秀、武本 佳昭、冨田 修平、仲谷 達也
    • Organizer
      第69回 日本泌尿器科学会 中部総会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2022-01-27  

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