Mechanisms of tumor-induced immune tolerance during the process of peritoneal dissemination of ovarian cancer

卵巢癌腹膜播散过程中肿瘤诱导的免疫耐受机制

• 批准号: 23592459
• 负责人: INO Kazuhiko
• 金额: $ 3.41万
• 依托单位: Wakayama Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23592459/
• 关键词: 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

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.

吲哚胺2,3-双加氧酶（IDO）是一种具有免疫调节功能的色氨酸分解酶。本研究的目的是阐明IDO在卵巢癌腹膜播散过程中的作用。将IDO-cDNA转染到小鼠卵巢癌细胞系HM-1中，建立ido过表达细胞（HM-1- ido）。将HM-1-IDO或模拟物腹腔内移植到同基因免疫功能小鼠体内。hm -1- ido移植小鼠的生存期明显缩短，肿瘤重量和腹水增加，肿瘤内CD8+ T细胞和NK细胞数量明显减少，腹水中tgf - β水平明显升高。这些数据表明，肿瘤IDO通过抑制肿瘤浸润性T和nk细胞募集以及增强腹水中免疫抑制细胞因子来促进卵巢癌的腹膜传播，因此IDO可能是卵巢癌治疗策略的一个有希望的分子靶点。

项目成果

Indoleamine 2,3-dioxygenase promotes peritoneal metastasis of ovarian cancer by inducing an immunosuppressive environment.

• DOI: 10.1111/cas.12445
• 发表时间: 2014-08
• 期刊: Cancer science
• 影响因子: 5.7
• 作者: Tanizaki Y;Kobayashi A;Toujima S;Shiro M;Mizoguchi M;Mabuchi Y;Yagi S;Minami S;Takikawa O;Ino K
• 通讯作者: Ino K

IDO and immune tolerance in ovarian cancer

IDO 与卵巢癌的免疫耐受

• 发表时间: 2011
• 期刊: Current Opinion Obstetrics and Gynecology
• 作者: Fujimoto T;Andoh T;Sudo T;Fujita I;Imbabura M;Moritake H;Sugimoto T;Sakuma Y;Takeuchi T;Sonobe H;Epstein AL;Akisue T;Kirihata M;Kurosaka M;Fukumori Y;Ichikawa H;Ino K
• 通讯作者: Ino K

High expression of N-acetylglucosaminyltransferase IVa promotes invasion of choriocarcinoma.

• DOI: 10.1038/bjc.2012.496
• 发表时间: 2012-12-04
• 期刊: BRITISH JOURNAL OF CANCER
• 影响因子: 8.8
• 作者: Niimi, K.;Yamamoto, E.;Fujiwara, S.;Shinjo, K.;Kotani, T.;Umezu, T.;Kajiyama, H.;Shibata, K.;Ino, K.;Kikkawa, F.
• 通讯作者: Kikkawa, F.

Monoclonality of composite large-cell neuroendocrine carcinoma and invasive intestinal-type mucinous adenocarcinoma of the cervix : a case study

复合性大细胞神经内分泌癌和宫颈浸润性肠型粘液性腺癌的单克隆性：病例研究

• DOI: 10.1097/pgp.0b013e318261c35b
• 发表时间: 2013
• 期刊: Int J Gynecol Pathol
• 影响因子: 2.4
• 作者: Yasuoka H;Tsujimoto M;Ueda M;Kodama R;Iwahashi Y;Inagaki M;Mabuchi Y;Ino K;Sanke T;Nakamura Y
• 通讯作者: Nakamura Y

免疫寛容分子IDOは卵巣癌腹膜播種を促進する

免疫耐受分子IDO促进卵巢癌腹膜播散

• 发表时间: 2012
• 作者: 谷﨑優子;小林彩;山本円;馬淵泰士;岩橋正明;南佐和子;井箟一彦
• 通讯作者: 井箟一彦