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Role of autophagy in immunoescape of solid tumor

Research Project

Project/Area Number 24659599
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Digestive surgery
Research InstitutionThe University of Tokyo

Principal Investigator

KITAYAMA JOJI  東京大学, 医学部附属病院, 准教授 (20251308)

Co-Investigator(Renkei-kenkyūsha) YAMASHITA Hiroharu  東京大学, 医学部付属病院, 助教 (50599397)
YAMAGUCHI Hironori  東京大学, 医学部付属病院, 助教 (20376445)
KAWAI Kazushige  東京大学, 医学部付属病院, 助教 (80571942)
Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords低酸素 / 低栄養 / autophagy
Research Abstract

We established a mouse model to investigate the local immune reaction in regeonal lymphnodes. Using this model, we found that Chloroquine, an autophagy inhibitor, significantly potentiated the antitumor activity of Temsirolimus in vitro and in vivo. The combination therapy triggered enhanced apoptosis, which corresponded to an increased Bax/Bcl-2 ratio. In human, we also found that a minor subset of intraperitoneal free cells with CD90(+)CD45(-) phenotype vigorously grow in culture with mesothelial-like morphology. Interestingly, these cultured cells were similar to mesenchymal stem cells (MSC), and were designated as intraperitoneal MSC (pMSC). The growth of pMSC is strongly inhibited by hypoxia or hypoglycemia possibly through autophagy.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (9 results)

All 2014 2013 2012 Other

All Journal Article (4 results) (of which Peer Reviewed: 1 results) Presentation (4 results) Remarks (1 results)

  • [Journal Article] Temsirolimus and chloroquine cooperatively exhibit a potent antitumor effect against colorectal cancer cells2014

    • Author(s)
      Kaneko M, Nozawa H, Hiyoshi M, Tada N, Murono K, Nirei T, Emoto S, Kishikawa J, Iida Y, Sunami E, Tsuno NH, Kitayama J, Takahashi K, Watanabe T
    • Journal Title

      J Cancer Res Clin Oncol

      Volume: 140(5) Pages: 769-81

    • Related Report
      2013 Final Research Report
  • [Journal Article] CD90+ mesothelial-like cells in peritoneal fluid promote peritoneal metastasis by forming a tumor permissive microenvironment2014

    • Author(s)
      Kitayama J, Emoto S, Yamaguchi H, Ishigami H, Watanabe T
    • Journal Title

      PLoS One

      Volume: 9(1)

    • Related Report
      2013 Final Research Report
  • [Journal Article] CD90(+)CD45(-) intraperitoneal mesothelial-like cells inhibit T cell activation by production of arginase I2014

    • Author(s)
      Kitayama J, Emoto S, Yamaguchi H, Ishigami H, Yamashita H, Seto Y, Matsuzaki K, Watanabe T
    • Journal Title

      Cell Immunol

      Volume: 288(1-2) Pages: 8-14

    • Related Report
      2013 Final Research Report
  • [Journal Article] Temsirolimus and chloroquine cooperatively exhibit a potent antitumor effect against colorectal cancer cells.2014

    • Author(s)
      Kaneko M
    • Journal Title

      J Cancer Res Clin Oncol.

      Volume: 140(5) Issue: 5 Pages: 769-81

    • DOI

      10.1007/s00432-014-1628-0

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] CD90+ mesothelial-like cells in peritoneal fluid promote peritoneal metastasis by forming a tumor permissive microenvironment2014

    • Author(s)
      Kitayama J, Emoto S, Yamaguchi H, Ishigami H, Watanabe T
    • Organizer
      104^<th> Annual meeting of American Association of Cancer Research
    • Place of Presentation
      SanDiego CA, USA
    • Year and Date
      2014-04-06
    • Related Report
      2013 Final Research Report
  • [Presentation] 胃癌腹膜播種の成立における腹腔内遊離間葉系幹細胞の役割とその臨床的意義2014

    • Author(s)
      北山丈二、江本成伸、山口博紀、石神浩徳、山下裕玄、瀬戸泰之、松﨑圭祐、渡邉聡明
    • Organizer
      第86回日本胃癌学会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] Temsirolimusは複数のメカニズムによって大腸癌の進展を抑制する(Temsirolimus suppresses colorectal cancer growth by multiple mechanisms)2013

    • Author(s)
      野澤宏彰
    • Organizer
      第72回日本癌学会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] Temsirolimusは複数のメカニズムによって大腸癌の進展を抑制する2012

    • Author(s)
      野澤宏彰, 北山丈二, 金子学, 津野ネルソン, 須並英二, 高橋孝喜, 渡邉聡明
    • Organizer
      第71回日本癌学会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Remarks] HP

    • URL

      http://all-1su.umin.jp/surgical/

    • Related Report
      2013 Final Research Report

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Published: 2013-05-31   Modified: 2019-07-29  

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