| Project/Area Number |
25462614
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Keio University |
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Principal Investigator |
Hiroshi Nishio 慶應義塾大学, 医学部, 特任助教 (90445239)
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| Co-Investigator(Kenkyū-buntansha) |
IWATA TAKASHI 慶應義塾大学, 医学部, 専任講師 (30296652)
谷口 智憲 慶應義塾大学, 医学部, 助教 (40424163)
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| Co-Investigator(Renkei-kenkyūsha) |
YAGUCHI TOMONORI 慶應義塾大学, 医学部, 助教 (40424163)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 卵巣がん / 免疫逃避 / HNF-1beta / NF-ｋB / STAT3 / 免疫抑制 / サイトカイン |
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| Outline of Final Research Achievements |
Cancer-induced immunosuppression is one of the major problems for development of cancer immunotherapies. A transcriptional factor HNF-1β preferentially activated in human ovarian clear cell cancer (OCCC) have been reported. We have investigated roles of HNF-1β in the immunosuppressive activity of human OCCC. HNF-1β knockdown and overexpression experiments revealed that HNF-1β induced immunosuppressive cytokine production. In vitro suppressive activities of human OCCC culture supernatants on dendritic cell were reduced by knockdown of HNF-1β in cancer cells. In the mice model, knockdown of HNF-1β in the cancer cells resulted in restoration of T cell stimulatory activity of murine splenic DC in spleens and tumors. Therefore, HNF-1β activation in human OCCC is an upstream event for induction of immunosuppression, and is an attractive target for restoring immunocompetence in OCCC patients.
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