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Mechanisms of cancer cell clonal expansion via phenotypic and spatial diversity in the cancer microenvironment.

Research Project

Project/Area Number 22K19527
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 53:Organ-based internal medicine and related fields
Research InstitutionOsaka University

Principal Investigator

Takehara Tetsuo  大阪大学, 大学院医学系研究科, 教授 (70335355)

Co-Investigator(Kenkyū-buntansha) 小玉 尚宏  大阪大学, 大学院医学系研究科, 助教 (10623275)
Project Period (FY) 2022-06-30 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2023: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2022: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Keywords膵癌 / 癌微小環境 / 多核球系骨髄由来免疫抑制細胞 / 慢性炎症
Outline of Research at the Start

本研究は、単一細胞空間的トランスクリプトミクス解析技術と細胞バーコーディングによるがん細胞のクローナリティ追跡技術を用いて、癌微小環境の多様性ががん細胞のクローン拡大に与える影響を解明することを目的とし、本研究を通じて癌微小環境を標的とした膵癌の新たな創薬を目指す。

Outline of Final Research Achievements

Disregulation of inflammation and the resulting triggering of phenotypic diversity of immune cells in the cancer microenvironment may be involved in the progression of pancreatic cancer and resistance to cancer immunotherapy, but this has not been investigated in detail. Therefore, we focused on the phenotypic and spatial diversity of the cancer microenvironment in pancreatic cancer with the aim of elucidating the pathogenesis and progression mechanisms of pancreatic cancer. Analysis of the cancer microenvironment in human and mouse pancreatic cancer revealed that the interaction between inflammation-based cancer cells, polymorphonuclear bone marrow-derived immunosuppressive cells and CD8 T cells is important in the progression of pancreatic cancer.

Academic Significance and Societal Importance of the Research Achievements

本研究により、膵臓内の組織微小環境で生じる慢性炎症が膵癌の発症や進展に与える影響が明らかとなり、その関係を繋ぐ重要な免疫細胞集団が同定されたことで、今後これらの細胞を標的とした治療薬開発に繋がる可能性が期待される。その結果非常に予後不良な膵癌患者の予後改善に寄与する可能性のある研究成果であり、その社会的意義は極めて大きいと考える。また、膵炎と膵癌を繋ぐ新たな分子機序の解明は、炎症と癌という近年注目されている学問領域の発展に寄与する研究成果であり、学術的にも重要な成果であると考えられる。

Report

(3 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • Research Products

    (4 results)

All 2023 2022

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

  • [Journal Article] Regnase-1 downregulation promotes pancreatic cancer through myeloid-derived suppressor cell-mediated evasion of anticancer immunity2023

    • Author(s)
      Okabe J, Kodama T, Sato Y, Shigeno S, Matsumae T, Daiku K, Sato K, Yoshioka T, Shigekawa M, Higashiguchi M, Kobayashi S, Hikita H, Tatsumi T, Okamoto T, Satoh T, Eguchi H, Akira S, Takehara T.
    • Journal Title

      J Exp Clin Cancer Res

      Volume: 9;42 Issue: 1 Pages: 262-262

    • DOI

      10.1186/s13046-023-02831-w

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pentraxin 3 is an adipose tissue‐related serum marker for pancreatic cancer cachexia predicting subsequent muscle mass and visceral fat loss2022

    • Author(s)
      Sato Katsuhiko、Hikita Hayato、Shigekawa Minoru、Kato Seiya、Sasaki Yoichi、Shinkai Kazuma、Fukuoka Makoto、Kudo Shinnosuke、Sato Yu、Fukumoto Kenji、Shirai Kumiko、Myojin Yuta、Sakane Sadatsugu、Murai Kazuhiro、Yoshioka Teppei、Nishio Akira、Kodama Takahiro、Sakamori Ryotaro、Tatsumi Tomohide、Takehara Tetsuo
    • Journal Title

      Cancer Science

      Volume: 113 Issue: 12 Pages: 4311-4326

    • DOI

      10.1111/cas.15569

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 炎症制御分子 Regnase-1 を介した膵がん発症・進展機構の解明2023

    • Author(s)
      岡部 純弥、小玉尚宏、竹原 徹郎
    • Organizer
      第54回日本膵臓学会大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] A novel mechanism of driving intrahepatic cholangiocarcinoma2023

    • Author(s)
      小玉尚宏
    • Organizer
      37th Meeting of the USJCMSP Hepatitis Panel.
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited

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Published: 2022-07-05   Modified: 2025-01-30  

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