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A study for immunological feature of tumor endothelial cells (TEC) in immune evasion mechanism of tumor micro-environment and development of a novel anti-cancer therapy

Research Project

Project/Area Number 25462008
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)

Co-Investigator(Renkei-kenkyūsha) OHDAN HIDEKI  国立大学法人 広島大学, 大学院医歯薬保健学研究院 消化器・移植外科学, 教授 (10363061)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords腫瘍免疫 / 免疫逃避 / 内皮細胞 / 微小環境 / クロストーク
Outline of Final Research Achievements

Although a remarkable progress in anti-cancer therapies, caner can be resistant to therapies in some situations, which could related 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 growing tumor in mice in which B16 melanoma cells had been implanted suppressed T cell proliferation in a dose-dependent manner. Further, tumor-endothelial cell serial culture assay revealed that immunosuppressive function of TEC required HMGB1 from tumor and exosome secreted from TEC had immunosuppressive activity. In vivo animal model, tumor growth was suppressed by local injection of anti-HMGB1 antibody. These results suggest that TECs contribute immune-evasion of tumor by acquiring immunosuppressive feature through cross-talk with tumor and blockade of this cross-talk could be a promising anti-cancer strategy.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (5 results)

All 2016 2015 2014 2013

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 1 results)

  • [Journal Article] Prophylactic managements of hepatitis B viral infection in liver transplantation.2016

    • Author(s)
      Onoe T, Tahara H, Tanaka Y, Ohdan H.
    • Journal Title

      World J Gastroenterol

      Volume: 22 Issue: 1 Pages: 165-175

    • DOI

      10.3748/wjg.v22.i1.165

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fc-Gamma Receptor Polymorphisms Predispose Patients to Infectious Complications After Liver Transplantation.2016

    • Author(s)
      Shimizu S, Tanaka Y, Tazawa H, Verma S, Onoe T, Ishiyama K, Ohira M, Ide K, Ohdan H.
    • Journal Title

      Am J Transplant.

      Volume: 16(2) Issue: 2 Pages: 625-633

    • DOI

      10.1111/ajt.13492

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Role of Liver Sinusoidal Endothelial Cells in Induction of Carbohydrate Reactive B Cells Tolerance Through the Programmed Death 1/Programmed Death Ligand 1 Pathway2015

    • Author(s)
      Igarashi Y, Onoe T, Ohdan H.
    • Journal Title

      Transplantation

      Volume: 99(11) Issue: 11 Pages: 2325-2336

    • DOI

      10.1097/tp.0000000000000831

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Xenograft tolerance and immune function of human T cells developing in pig thymus xenografts.2014

    • Author(s)
      Kalscheuer H, Onoe T, Dahmani A, Li HW, Hölzl M, Yamada K, Sykes M.
    • Journal Title

      J Immunol

      Volume: 192(7) Issue: 7 Pages: 3442-3450

    • DOI

      10.4049/jimmunol.1302886

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Conditional ablation of HMGB 1 in mice reveals its protective function a gainst endotoxemia and bacterial infection2013

    • Author(s)
      Yanai, H, et al.
    • Journal Title

      Proc. Natl. Acad. Sci. U S A.

      Volume: 51 Issue: 51 Pages: 20699-20704

    • DOI

      10.1073/pnas.1320808110

    • Related Report
      2013 Research-status Report
    • Peer Reviewed

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Published: 2014-07-25   Modified: 2019-07-29  

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