Analyses of tumor heterogeneity and peritoneal tumor microenvironment in ovarian cancer for development of novel tumor immunotherapy

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K20138
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: Nagoya University
• Principal Investigator: SUZUKI Shiro 名古屋大学, 医学部附属病院, 講師 (20612758)
• Research Collaborator: NAKATSURA Tetsuya 国立がん研究センター, 先端医療開発センター, 免疫療法開発分野長
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 卵巣がん / 腹膜播種

Outline of Final Research Achievements

We established a subclone of ID8 mouse ovarian cancer cell line (ID8-T6) which more quickly forms peritoneal dissemination. IL-33 was up-regulated in both ID8-T6 cells and tissue compared with for ID8. We confirmed the expression of IL-33 in human epithelial ovarian cancer (EOC) cell lines. Unexpectedly, the survival rate of IL33-overexpressing subclone (ID8-IL33) tumor-bearing mice was significantly prolonged compared with that of ID8-mock tumor-bearing mice. Infiltrating CD4+ cells and CD8+ cells within the disseminated tumor tissues were significantly increased in ID8-IL33 tumors compared with in ID8-mock tumors. In contrast, myeloid-derived suppressor cells (MDSCs) were significantly decreased in IL33-overexpressing tumors. Ascites from ID8-IL33 tumor-bearing mice inhibited MDSC differentiation. EOC patients with high staining of IL-33 had significantly longer overall survival times.
We also established ID8 chemo-resistant subclones and heterogeneity assessment mouse models.

Free Research Field

産婦人科学