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

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.