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Elucidation of Human Cancer Immunity Based on Analysis of CXCL13-Producing T Cells in the Cancer Microenvironment

Research Project

Project/Area Number 20K20610
Research Category

Grant-in-Aid for Challenging Research (Pioneering)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
Research InstitutionKyoto University

Principal Investigator

Yoshitomi Hiroyuki  京都大学, 医学研究科, 准教授 (50402920)

Co-Investigator(Kenkyū-buntansha) 上野 英樹  京都大学, 医学研究科, 教授 (50850442)
濱西 潤三  京都大学, 医学研究科, 准教授 (80378736)
Project Period (FY) 2020-07-30 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥26,000,000 (Direct Cost: ¥20,000,000、Indirect Cost: ¥6,000,000)
Fiscal Year 2023: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2022: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2021: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2020: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
KeywordsT細胞 / CXCL13 / PD-1 / 子宮体がん / がん微小環境 / T細胞分化 / Tph細胞 / 炎症性サイトカイン / B細胞 / 症性サイトカイン
Outline of Research at the Start

申請者はこれまでにヒト検体を用いた研究より、炎症環境下でケモカインCXCL13を産生する新たなCD4T細胞分画(Tph細胞)を同定しその機能を明らかにしてきた。本研究ではこれまでのT細胞研究をがん免疫研究に応用し、がん組織に存在するCXCL13を産生するCD4およびCD8陽性T細胞の分子機構を解明する。これらの細胞のがん抗原特異性とともに表現型や抗がん作用を明らかにすることを目的とし、さらにその分化機構と抗がん作用を制御することで新たながん治療をめざす。

Outline of Final Research Achievements

We performed scRNA-seq analysis of T cells from uterine cancer tissues and showed that PD-1+CD39+CD103+CD8+ T cells produce CXCL13 in cancer tissues. Furthermore, we integrated and compared scRNA-seq data of rheumatoid arthritis synovial T cells to analyze the microenvironment in cancer tissues and its effect on T cell differentiation. Intensive oligoclonal proliferation was observed in PD-1+CXCL13+ CD8+ T cells. We also identified a FoxP3+CD8+ T cell population and showed that this TCR is highly shared with PD-1+CXCL13+CD8+ T cells.

Academic Significance and Societal Importance of the Research Achievements

本研究の成果は申請者がこれまで行ってきたヒト検体を用いた炎症環境下におけるT細胞研究をがん免疫に応用し、ヒトがん微小環境に存在するT細胞で上昇しているパスウエイや、それらがT細胞分化に及ぼす影響を明らかにした。さらにTCRクロノタイプ解析より、PD-1+CXCL13+CD8+T細胞が高度にオリゴクローナルな増殖をきたすこと、一部がFOXP3+CD8+T細胞とT細胞受容体配列を共有することを示した。マウスのT細胞はCXCL13を産生しないことが知られており、CXCL13を産生するヒトT細胞にアプローチする本研究の成果はマウスモデルではすすめることが困難な独創性の高いものである。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (6 results)

All 2023 2022 2020

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (2 results)

  • [Journal Article] Peripheral helper T cells, mavericks of peripheral immune responses2023

    • Author(s)
      Yoshitomi Hiroyuki
    • Journal Title

      International Immunology

      Volume: 36 Issue: 1 Pages: 9-16

    • DOI

      10.1093/intimm/dxad041

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CXCL13-producing CD4+ T cells accumulate in the early phase of tertiary lymphoid structures in ovarian cancer2022

    • Author(s)
      Ukita Masayo、Hamanishi Junzo、Yoshitomi Hiroyuki、Yamanoi Koji、Takamatsu Shiro、Ueda Akihiko、Suzuki Haruka、Hosoe Yuko、Furutake Yoko、Taki Mana、Abiko Kaoru、Yamaguchi Ken、Nakai Hidekatsu、Baba Tsukasa、Matsumura Noriomi、Yoshizawa Akihiko、Ueno Hideki、Mandai Masaki
    • Journal Title

      JCI Insight

      Volume: 7 Issue: 12 Pages: 157215-157215

    • DOI

      10.1172/jci.insight.157215

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Shared and distinct roles of T peripheral helper and T follicular helper cells in human diseases2020

    • Author(s)
      Yoshitomi Hiroyuki、Ueno Hideki
    • Journal Title

      Cellular & Molecular Immunology

      Volume: 18 Issue: 3 Pages: 523-527

    • DOI

      10.1038/s41423-020-00529-z

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] CXCL13-producing PD-1hiCXCR5? helper T cells in chronic inflammation2020

    • Author(s)
      Yoshitomi Hiroyuki
    • Journal Title

      Immunological Medicine

      Volume: 43 Issue: 4 Pages: 156-160

    • DOI

      10.1080/25785826.2020.1781998

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] Tfh細胞によるオリゴクローナルなIgG+形質細胞は子宮体癌の良好な予後と相関する2022

    • Author(s)
      藤岡麻友
    • Organizer
      第81回日本癌学会学術総会
    • Related Report
      2022 Research-status Report
  • [Presentation] Clonal expanded IgG-producing plasma cells triggered by Tfh cells are associated with better survival in endometrial cancer2022

    • Author(s)
      Mayu Fujioka
    • Organizer
      第51回日本免疫学会学術集会
    • Related Report
      2022 Research-status Report

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Published: 2020-08-03   Modified: 2025-01-30  

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