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Exploring a mechanism of tumor immunosuppresion induced by cancer-associated fibroblats

Research Project

Project/Area Number 16K10499
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Digestive surgery
Research InstitutionOkayama University

Principal Investigator

Noma Kazuhiro  岡山大学, 大学病院, 助教 (10534761)

Research Collaborator KATO takuya  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords癌関連線維芽細胞 / 腫瘍内リンパ球 / インターロイキン / 食道癌 / 腫瘍内浸潤リンパ球 / IL-6 / 腫瘍免疫抑制 / CAFs / esophageal cancer / TILs / tumor immunosuppression / interleukin 6 / がん微小環境 / がん関連線維芽細胞 / 腫瘍免疫 / 光線免疫療法 / 線維芽細胞 / 細胞標的治療
Outline of Final Research Achievements

Cancer-associated fibroblasts (CAFs) have been considered to have a central role for tumor progression in tumor microenvironment. We identified that intra-tumoral CD8+ and FoxP3+ tumor-infiltrating lymphocytes (TILs) are independent prognostic factors in esophageal cancer tissue of clinical samples. In addition, CAFs had a significant correlation of those TILs in intra-tumoral, but not peri-tumoral sites, so that CAFs regulated the infiltration of CD8+ and FoxP3+ TILs into intra-tumor tissues. In vitro, CAFs activated by cancer cells secreted high levels of Interleukin 6 (IL-6). In vivo, CAFs accelerated tumor growth obviously in immune-competent mice, along with phenotypic change in T cell populations, decreased CD8+ and increased FoxP3+ TILs. Moreover, the accelerated tumor growth in CAFs co-cultures was significantly reduced by IL-6 blockade, demonstrating that immunosuppressive TILs population was improved.

Academic Significance and Societal Importance of the Research Achievements

以上の結果は,腫瘍においてCAFsがリンパ球の浸潤をIL-6を用いて制御していることの解明に繋がった.IL-6は元来炎症性サイトカインであり腫瘍に対する影響はあまり報告がない.我々の発見した知見より,現在抗リウマチ薬として市販されている抗IL-6抗体やその他のIL-6阻害剤が癌の治療、すなわち腫瘍内のリンパ球の組成を改善し,腫瘍制御につながる可能性を示している.いわゆるドラッグリポジショニングの一つの可能性を示し医療経済的にも非常に有意義な研究結果である.

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (14 results)

All 2018 2017 2016

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (13 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Cancer-Associated Fibroblasts Affect Intratumoral CD8+ and FoxP3+ T Cells Via IL6 in the Tumor Microenvironment.2018

    • Author(s)
      Kato T, Noma K, Ohara T, Kashima H, Katsura Y, Sato H, Komoto S, Katsube R, Ninomiya T, Tazawa H, Shirakawa Y, Fujiwara T.
    • Journal Title

      Clinical Cancer Research

      Volume: 24(19) Pages: 4820-4833

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] Cancer-associated fibroblasts affect the intra-tumoral infiltration of CD8+ and FoxP3+ T cells via IL-6.2018

    • Author(s)
      Takuka Kato, Kazuhiro Noma, et al.
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 癌関連線維芽細胞が引き起こす腫瘍免疫抑制の解明 ―腫瘍浸潤リンパ球とIL-6と代謝の観点から―2018

    • Author(s)
      加藤卓也、野間和広 他
    • Organizer
      第22回日本がん免疫学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 癌関連線維芽細胞は腫瘍浸潤リンパ球を制御することにより食道癌の予後に寄与する2018

    • Author(s)
      加藤卓也、野間和広 他
    • Organizer
      第72回日本食道学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Cancer-associated fibroblasts regulate intratumoral CD8+/FoxP3+ T cells via interleukin 6 in the tumor immune microenvironment.2018

    • Author(s)
      Takuka Kato, Kazuhiro Noma, et al.
    • Organizer
      The 109th American Association for Cancer Research Annual Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Cancer-associated fibroblasts (CAFs) contribute to tumor immunosuppression by regulating tumor-infiltrating lymphocytes2017

    • Author(s)
      Takuya Kato, Kazuhiro Noma, Toshiyoshi Fujiwara, et al.
    • Organizer
      American Association of Cancer Research
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 癌関連線維芽細胞は腫瘍浸潤リンパ球を制御することにより腫瘍免疫抑制を調整する2017

    • Author(s)
      加藤卓也,野間和広、藤原俊義ほか
    • Organizer
      第38回日本癌免疫外科学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 癌関連線維芽細胞はIL-6を介しTILsを制御し腫瘍免疫を抑制する2017

    • Author(s)
      加藤卓也,野間和広、藤原俊義ほか
    • Organizer
      第26回日本がん転移学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 癌関連線維芽細胞(CAFs)により放出されるIL-6が腫瘍免疫抑制を引き起こす2017

    • Author(s)
      加藤卓也,野間和広、藤原俊義ほか
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 癌関連線維芽細胞による腫瘍免疫抑制と腫瘍浸潤リンパ球制御の同定2017

    • Author(s)
      加藤卓也,野間和広、藤原俊義ほか
    • Organizer
      第30回日本バイオセラピィ学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 癌関連線維芽細胞と腫瘍浸潤リンパ球の関連性について ー食道癌手術標本とマウス皮下腫瘍モデルの検討ー2016

    • Author(s)
      加藤卓也
    • Organizer
      日本バイオセラピィ学会
    • Place of Presentation
      久留米市
    • Year and Date
      2016-12-01
    • Related Report
      2016 Research-status Report
  • [Presentation] The elucidation of the tumor immunosuppression affected by cancer-associated fibroblasts (CAFs) in esophageal cancer2016

    • Author(s)
      加藤卓也
    • Organizer
      日本癌学会
    • Place of Presentation
      横浜市
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
  • [Presentation] cancer associated fibroblasts(CAFs)と腫瘍免疫抑制の解明―CAFs 特異的光線免疫療法の臨床応用にむけて―2016

    • Author(s)
      加藤卓也
    • Organizer
      癌免疫外科研究会
    • Place of Presentation
      川越市
    • Year and Date
      2016-05-12
    • Related Report
      2016 Research-status Report
  • [Presentation] The Prognostic correlation of tumor-infiltrating lymphocytes (TILs) and cancer associated fibroblasts (CAFs) in patients with human esophageal carcinoma2016

    • Author(s)
      Takuya Kato
    • Organizer
      AACR 2016
    • Place of Presentation
      New Orleans, Louisiana
    • Year and Date
      2016-04-16
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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