The mechanisms of immune-mediated tumor progression triggered by cancer metabolism

• Project/Area Number: 26670183
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology
• Research Institution: Keio University
• Principal Investigator: Jinushi Masahisa 慶應義塾大学, 医学部, 准教授 (40318085)
• Research Collaborator: Kitabayashi Isho 国立がん研究センター, 研究所, 造血腫瘍分野長 ; Kimohara Yoshihiro 熊本大学, 大学院医学研究科細胞病理学, 准教授 ; Taku syuichiro 熊本大学, 大学院医学研究科脳神経外科学, 講師 ; Akita Hirotoshi 北海道大学, 大学院医学研究科腫瘍内科学, 教授 ; Yagita Hideo 順天堂大学, 医学部免疫学, 先任准教授
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 腫瘍代謝 / 癌 / 代謝 / 免疫 / IDH(R132H)

Outline of Final Research Achievements

I focused the role of most notable cancer metabolic pathway, IDH1/2 mutation in gliomas on tumor immunogenic phenotypes, I found that IDH1/2 in glioma cells contribute to generation of immunosuppressive microenvironments, which are manifested by the infiltration of M2 macrophages, MDSCs, and PD-1-positive T cells with transformation of PD-L1-positive glioma cells from PD-L1-bnegative ones. Thus, IDH-1/2 mutation triggers "inflamed phanotypes" of gliomas, and our study provides scientific rationale that immunochenckpoint blackade may be useful for targeting IDH-mutated tumors.

Research Products

• [Journal Article] Induction of protumoral CD11c[high] macrophages by glioma cancer stem cells thorough GM-CSF (2016)
  • Author(s): Kokubu et al
  • Journal Title: Genes to Cells Volume: 21 Issue: 3 Pages: 241-251
  • DOI: 10.1111/gtc.12333
  • Peer Reviewed
• [Journal Article] MFG-E8 Is Critical for Embryonic Stem Cell-Mediated T Cell Immunomodulation. (2015)
  • Author(s): Tan Y, AlKhamees B, Jia D, Li L, Couture JF, Figeys D, Jinushi M, Wang L.
  • Journal Title: Stem Cell Reports Volume: 5(5) Pages: 741-52
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The coordinated actions of TIM-3 on cancer and myeloid cells in the regulation of tumorigenicity and clinical prognosis in clear cell renal cell carcinomas (2015)
  • Author(s): Yoshihiro Komohara, Tomoko Morita, Dorcas A. Annan, Hasita Horlad, Koji Ohnishi, Sohsuke Yamada, Toshiyuki Nakayama, Shohei Kitada, Shinya Suzu, Ichiro Kinoshita, Hirotoshi Dosaka-Akita, Koichi Akashi, Motohiro Takeya, Masahisa Jinushi
  • Journal Title: Cancer immunology research Volume: 3 Issue: 9 Pages: 999-1007
  • DOI: 10.1158/2326-6066.cir-14-0156
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Tumor-associated macrophages as an emerging target against tumors: Creating a new path from bench to bedside. (2015)
  • Author(s): Jinushi M, Komohara Y
  • Journal Title: Biochim Biophys Acta. Volume: 1855 Issue: 2 Pages: 123-130
  • DOI: 10.1016/j.bbcan.2015.01.002
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Low expression levels of microRNA-124-5p correlated with poor prognosis in colorectal cancer via targeting of SMC4. (2014)
  • Author(s): Jinushi T, Shibayama Y, Kinoshita I, Oizumi S, Jinushi M, Aota T, Takahashi T, Horita S, Dosaka-Akita H, Iseki K.
  • Journal Title: Cancer Medicine Volume: 3 Issue: 6 Pages: 1544-1552
  • DOI: 10.1002/cam4.309
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Immune regulation of therapy-resistant niches: emerging targets for improving anticancer drug responses. (2014)
  • Author(s): Jinushi M
  • Journal Title: Cancer and Metastasis Review Volume: 33 Issue: 2-3 Pages: 737-745
  • DOI: 10.1007/s10555-014-9501-9
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Cancer stem-like cells derived from chemoresistant tumors have a unique capacity to prime tumorigenic myeloid cells. (2014)
  • Author(s): Yamashina T, Baghdadi M, Yoneda A, Kinoshita I, Suzu S, Dosaka-Akita H, Jinushi M.
  • Journal Title: Cancer Research Volume: 74 Issue: 10 Pages: 2698-2709
  • DOI: 10.1158/0008-5472.can-13-2169
  • Peer Reviewed / Acknowledgement Compliant