| Project/Area Number |
24592532
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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 |
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| Co-Investigator(Kenkyū-buntansha) |
KAWAKAMI Yutaka 慶應義塾大学, 医学部, 教授 (50161287)
IWATA Takasi 慶應義塾大学, 医学部, 講師 (30296652)
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| Co-Investigator(Renkei-kenkyūsha) |
AOKI Daisuke 慶應義塾大学, 医学部, 教授 (30167788)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 卵巣明細胞腺癌 / HNF-1beta / がん微小環境 / がん免疫抑制 / 癌 / がん免疫 / 卵巣癌 / 癌微小環境 |
|---|
| Outline of Final Research Achievements |
Hepatocyte nuclear factor-1beta (HNF-1beta) is a transcription factor and is overexpressed in ovarian clear cell carcinoma (OCCC). Here, we investigated immunosuppressive roles of HNF-1beta in OCCC. IL-6 production and activation of NF-kB and STAT3 was associated with HNF-1beta accumulation in OCCC cell lines. Culture supernatants (CS) from HNF-1beta accumulated OCCC have activities to impair dendritic cells (DCs) maturation. These immunosuppressive CS activity was reduced by knocking down HNF-1beta, partly owing to down-regulation of IL-6. Murine splenic, lymphnode and tumor-infiltrating DCs obtained from nude mice implanted with HNF-1beta knocking down OCCC cells restored activity to activate T cell than did DCs from control OCCC cells. These results indicate that HNF-1beta in OCCC may be involved in the immunosuppression mediated by impaired DC, and is not only useful as the tumor marker but also attractive targets for restoring immunocompetence in patients with OCCC.
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