Regulatory T cells, inherited variation, and clinical outcome in epithelial ovarian cancer.
Regulatory T cells, inherited variation, and clinical outcome in epithelial ovarian cancer.
复制标题
DOI：
10.1007/s00262-015-1753-x
复制
发表时间：
2015-12
期刊：
影响因子：
--
通讯作者：
Goode EL
中科院分区：
文献类型：
--
作者：
Knutson KL;Maurer MJ;Preston CC;Moysich KB;Goergen K;Hawthorne KM;Cunningham JM;Odunsi K;Hartmann LC;Kalli KR;Oberg AL;Goode EL
免疫系统是改变卵巢癌预后的宿主因素之一。调节性T细胞（Tcells）被认为是阻止免疫反应破坏卵巢癌的主要因素。了解调节肿瘤微环境中TGFAP的机制可能会导致识别旨在减少其影响的新靶点。在这项研究中，我们使用基于免疫荧光的显微镜对来自400多名卵巢癌患者（> 80%的高级别浆液性）的新鲜冷冻肿瘤中的T细胞、总CD 4 T细胞和CD 8+细胞毒性T细胞进行计数。我们试图确定TcR是否与已知影响Treg诱导，运输或功能的79个基因的生存和遗传变异相关。我们使用考克斯回归，考虑已知的预后因素，估计与T细胞计数和比率相关的风险比（HR）。我们发现，CD 8 T细胞和总CD 4 T细胞与T细胞的比率与改善的总体存活率（CD 8/Treg HR 0.84，p = 0.0089; CD 4/Treg HR 0.88，p = 0.046）和IL-10的遗传变异（分别为p = 0.0073和0.01）相关。在多变量分析中，比值和总生存期之间的相关性保持相似（IL-10和临床协变量调整的CD 8/Treg HR 0.85，p = 0.031; CD 4/Treg HR 0.87，p = 0.093），表明该相关性不是由IL-10的变化驱动的。因此，将新的肿瘤表型测定与广泛的临床和遗传信息相结合表明，T细胞与TcB的比率可能是卵巢癌预后的预后指标，而与TcB相关基因的遗传基因型无关。
The immune system constitutes one of the host factors modifying outcomes in ovarian cancer. Regulatory T cells (Tregs) are believed to be a major factor in preventing the immune response from destroying ovarian cancers. Understanding mechanisms that regulate Tregs in the tumor microenvironment could lead to the identification of novel targets aimed at reducing their influence. In this study, we used immunofluorescence-based microscopy to enumerate Tregs, total CD4 T cells, and CD8+ cytotoxic T cells in fresh frozen tumors from over 400 patients with ovarian cancer (>80 % high-grade serous). We sought to determine whether Tregs were associated with survival and genetic variation in 79 genes known to influence Treg induction, trafficking, or function. We used Cox regression, accounting for known prognostic factors, to estimate hazard ratios (HRs) associated with T cell counts and ratios. We found that the ratios of CD8 T cells and total CD4 T cells to Tregs were associated with improved overall survival (CD8/Treg HR 0.84, p = 0.0089; CD4/Treg HR 0.88, p = 0.046) and with genetic variation in IL-10 (p = 0.0073 and 0.01, respectively). In multivariate analyses, the associations between the ratios and overall survival remained similar (IL-10 and clinical covariate-adjusted CD8/Treg HR 0.85, p = 0.031; CD4/Treg HR 0.87, p = 0.093), suggesting that this association was not driven by variation in IL-10. Thus, integration of novel tumor phenotyping measures with extensive clinical and genetic information suggests that the ratio of T cells to Tregs may be prognostic of outcome in ovarian cancer, regardless of inherited genotype in genes related to Tregs.