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A study for novel mechanism underlying tumor immune-evasion through tumor endothelial cells as immune suppressive antigen presenting cells

Research Project

Project/Area Number 17K10573
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General surgery
Research InstitutionDepartment of Clinical Research, National Hospital Organization Kure Medical Center

Principal Investigator

Onoe Takashi  独立行政法人国立病院機構(呉医療センター臨床研究部), その他部局等, その他 (90549809)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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癌免疫 / 腫瘍血管内皮細胞 / 微小環境 / 免疫逃避 / PD-L1 / 腫瘍免疫 / 腫瘍内皮細胞 / 癌微小環境
Outline of Final Research Achievements

Although a remarkable progress in anti-cancer therapies, caner can be resistant to therapies in some situations, which could relate to immune-evasion of cancer. In this study, we evaluated an immunological feature of tumor endothelial cells (TEC) in immune evasion mechanism of tumor micro-environment. In vitro assay revealed that TECs from tumor of implanted B16 melanoma cells 1) are antigen presenting cell, 2) suppress CD8+ T cells proliferation and cytotoxicity throuth PD-1/PD-L1 pathway in antigen-specific manner and 3) induce immune-suppressive CD4+ T cells via IL-10 and TGF-b. Further, in vivo mouse model using PD-L1 knock out mice revealed that PD-L1 on TECs largely contribute to tumor progression. These results suggest that TECs largely contribute to immune-evasion of cancer.

Academic Significance and Societal Importance of the Research Achievements

現在,医学の進歩により癌も根治可能となってきたが治療に難渋する場合も多い。その背景には、癌の持つ免疫逃避機構が関与していると考えられる。この免疫逃避機構構築には、癌微小環境が大きく影響していると考えられる。本研究では、癌微小環境の一部である腫瘍血管内皮細胞の免疫学的側面に注目し解析を行い、腫瘍免疫細胞が癌微小環境の中で免疫抑制性を持ち、免疫チェックポイント分子であるPD-L1分子を介して癌免疫を抑制していることが明らかとなった。この結果は腫瘍内皮細胞そのものおよび癌とのクロストークの遮断が将来有望な新規癌治療戦略となりうることを示唆する。

Report

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

    (7 results)

All 2020 2019 2018 2017 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (4 results) (of which Int'l Joint Research: 2 results) Remarks (1 results)

  • [Journal Article] Tumor endothelial cell-mediated antigen-specific T-cell suppression via the PD-1/PD-L1 pathway2020

    • Author(s)
      Taguchi Kazuhiro、Onoe Takashi、Yoshida Tomoaki、Yamashita Yoshinori、Tanaka Yuka、Ohdan Hideki
    • Journal Title

      Molecular Cancer Research

      Volume: - Issue: 9 Pages: 1427-1440

    • DOI

      10.1158/1541-7786.mcr-19-0897

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Isolation of tumor endothelial cells from murine cancer2019

    • Author(s)
      Taguchi Kazuhiro、Onoe Takashi、Yoshida Tomoaki、Yamashita Yoshinori、Taniyama Kiyomi、Ohdan Hideki
    • Journal Title

      Journal of Immunological Methods

      Volume: 464 Pages: 105-113

    • DOI

      10.1016/j.jim.2018.11.005

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed
  • [Presentation] 腫瘍血管内皮細胞を介した腫瘍の免疫逃避機構の解明と新規抗がん治療の探索2019

    • Author(s)
      田口和浩
    • Organizer
      第119回 日本外科学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Novel mechanism underlying tumor immune-evasion across through tumor endothelial cells2018

    • Author(s)
      Taguchi Kazuhiro、Onoe Takashi
    • Organizer
      AACR(American Association of Cancer Research) 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Novel mechanism underlying tumor immune evasion through tumor endothelial cells2018

    • Author(s)
      田口 和弘
    • Organizer
      American Association for Cancer Research 2018
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 腫瘍血管内皮細胞を介した腫瘍の免疫逃避機構の解明2017

    • Author(s)
      田口 和弘
    • Organizer
      2017年 癌免疫学会
    • Related Report
      2017 Research-status Report
  • [Remarks] 呉医療センター・中国がんセンター 臨床研究部 研究室の活動内容

    • URL

      https://kure.hosp.go.jp/department/clinical_research/

    • Related Report
      2019 Annual Research Report

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

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