Immunomodulation of ovarian clear cell carcinoma by targeting HNF-1 beta pathway

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K10731
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Keio University
• Principal Investigator: Fujita Tomonobu 慶應義塾大学, 医学部(信濃町), 助教 (20199334)
• Co-Investigator(Kenkyū-buntansha): 岩田 卓 慶應義塾大学, 医学部(信濃町), 講師 (30296652) ; 河上 裕 慶應義塾大学, 医学部(信濃町), 教授 (50161287)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 卵巣癌 / 免疫療法

Outline of Final Research Achievements

We have evaluated immunopathology of human ovarian clear cell carcinoma (OCCC), which generally produces high amounts of immunosuppressive cytokines such as IL6 and IL8, which are correlated with poor prognoses. T cell infiltration in tumors is fewer in OCCC than that in serous ovarian cancers. We screened drug libraries and found twelve chemical compounds capable of inhibiting production of IL6 by OCCC cell lines. One of them epigenetically suppressed HNF-1β, an OCCC-specific transcriptional factor which we previously identified as the upstream for the high production of IL6 and IL8 from OCCC. Some of them also showed reversal of the immunosuppressive conditions in mice implanted with human OCCC cell lines. These results indicate that inhibitors on the HNF-1β-IL6/IL8 pathway may improve immunosuppressive conditions of OCCC and useful for combination immunotherapy for patients with OCCC.

Free Research Field

腫瘍免疫学