Role of autophagy in immunoescape of solid tumor

• Project/Area Number: 24659599
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Digestive surgery
• Research Institution: The 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: ¥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.

Research Products

• [Journal Article] Temsirolimus and chloroquine cooperatively exhibit a potent antitumor effect against colorectal cancer cells (2014)
  • 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
• [Journal Article] CD90+ mesothelial-like cells in peritoneal fluid promote peritoneal metastasis by forming a tumor permissive microenvironment (2014)
  • Author(s): Kitayama J, Emoto S, Yamaguchi H, Ishigami H, Watanabe T
  • Journal Title: PLoS One Volume: 9(1)
• [Journal Article] CD90(+)CD45(-) intraperitoneal mesothelial-like cells inhibit T cell activation by production of arginase I (2014)
  • 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
• [Journal Article] Temsirolimus an d 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) Pages: 769-781
  • DOI: 10.1007/s00432-014-1628-0
  • Peer Reviewed
• [Presentation] CD90+ mesothelial-like cells in peritoneal fluid promote peritoneal metastasis by forming a tumor permissive microenvironment (2014)
  • 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
• [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
• [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
• [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
• [Remarks] HP
  • URL: http://all-1su.umin.jp/surgical/