2014 Fiscal Year Final Research Report
Immunosuppressive roles of HNF-1beta in ovarian clear cell carcinoma (OCCC)
| Project/Area Number |
24592532
|
|---|
| 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 |
|
|---|
| 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)
|
|---|
| Co-Investigator(Renkei-kenkyūsha) |
AOKI Daisuke 慶應義塾大学, 医学部, 教授 (30167788)
|
|---|
| Project Period (FY) |
2012-04-01 – 2015-03-31
|
| Keywords | 卵巣明細胞腺癌 / HNF-1beta / がん微小環境 / がん免疫抑制 |
|---|
| 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.
|
| Free Research Field |
がん免疫学
|
