Project/Area Number |
23592459
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Obstetrics and gynecology
|
Research Institution | Wakayama Medical University |
Principal Investigator |
INO Kazuhiko 和歌山県立医科大学, 医学部, 教授 (60303640)
|
Co-Investigator(Kenkyū-buntansha) |
MABUCHI Yasushi 和歌山県立医科大学, 医学部, 助教 (80382357)
|
Project Period (FY) |
2011 – 2013
|
Project Status |
Completed (Fiscal Year 2013)
|
Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2012: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2011: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
|
Keywords | 卵巣癌 / 腫瘍免疫 / 免疫寛容 / 腹膜播種 / マウスモデル / 酵素 / 卵巣がん / 免疫療法 |
Research Abstract |
Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-catabolizing enzyme that has immunoregulatory functions. The purpose of the present study is to clarify the role of IDO during the process of peritoneal dissemination of ovarian cancer. IDO-cDNA was transfected into the murine ovarian carcinoma cell line HM-1, establishing IDO-overexpressing cells (HM-1-IDO). HM-1-IDO or mock were intraperitoneally transplanted into syngeneic immunocompetent mice. HM-1-IDO-transplanted mice showed significantly shortened survival, and increased tumor weight and ascites with the significantly reduced numbers of CD8+ T cells and NK cells within tumors as well as increased levels of TGF-beta in ascites. These data show that tumoral IDO promotes the peritoneal dissemination of ovarian cancer through suppression of tumor-infiltrating T and NK-cell recruitment and enhancement of immunosuppressive cytokines in ascites, thus IDO may be a promising molecular target for the therapeutic strategy of ovarian cancer.
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