Follicular regulatory T cells infiltrated the ovarian carcinoma and resulted in CD8 T cell dysfunction dependent on IL-10 pathway
Follicular regulatory T cells infiltrated the ovarian carcinoma and resulted in CD8 T cell dysfunction dependent on IL-10 pathway
复制标题
卵泡调节性T细胞浸润卵巢癌并依赖IL-10通路导致CD8 T细胞功能障碍
DOI：
10.1016/j.intimp.2018.12.051
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发表时间：
2019-03-01
影响因子：
5.6
通讯作者：
Xu, Yuan
中科院分区：
文献类型：
--
作者：
Li, Li;Ma, Yan;Xu, Yuan
卵巢癌患者Treg/CD8 T细胞比值高与患者预后呈负相关。人类滤泡调节性T （Tfr）细胞是一种新发现的Treg细胞亚群，具有滤泡辅助性T （Tfh）细胞（CXCR5(+)）和典型Treg细胞(CD25（+) Foxp3(+)）的特征。Tfr细胞在卵巢癌中的作用尚不清楚。我们发现，在外周血中，卵巢癌患者CD4(+) CD25(+) CD127(-) CXCR5(+) T细胞和CD4(+) CD25(+) CD127(-) CXCR5(+) Foxp3(+) T细胞水平均显著高于健康对照组。在切除的肿瘤样本中，Tfr细胞在淋巴细胞中所占的比例远高于外周血。有趣的是，来自卵巢癌患者的循环Tfr细胞的TGFB1和IL10的表达明显高于直接离体的健康对照，刺激后IL10的表达也明显高于健康对照。浸润肿瘤的Tfr细胞TGFB1和IL10的表达进一步上调。此外，Tfr细胞表达TGFB1和IL10水平与IFNG在肿瘤浸润性CD8 T细胞中的表达呈负相关。在体外CD8 T细胞/Tfr细胞共培养系统中，我们发现Tfr细胞可以显著抑制CD8 T细胞的激活，其方式依赖于IL-10，可能也依赖于tgf - β。总的来说，我们的研究发现Tfr细胞可以抑制CD8 T细胞，并且在卵巢癌患者中，Tfr细胞的频率和功能都有所增加。
A high Treg/CD8 T cell ratio in ovarian carcinoma was negatively associated with the prognosis of the patients. The human follicular regulatory T (Tfr) cells are a newly characterized subset of Treg cells with features of both follicular helper T (Tfh) cells (CXCR5(+)) and canonical Treg cells (CD25(+) Foxp3(+)). The role of Tfr cells in ovarian cancer is yet unclear. We found that in peripheral blood, the ovarian cancer patients presented significantly higher levels of both CD4(+) CD25(+) CD127(-) CXCR5(+) T cells and CD4(+) CD25(+) CD127(-) CXCR5(+) Foxp3(+) T cells than the healthy controls. In resected tumor samples, Tfr cells represented a much greater percentage of lymphocytes than in peripheral blood. Interestingly, the circulating Tfr cells from ovarian cancer patients presented significantly higher TGFB1 and IL10 expression than their counterparts in healthy controls directly ex vivo, and significantly higher IL10 after stimulation. The tumor-infiltrating Tfr cells presented further upregulated expression of TGFB1 and IL10. In addition, the levels of TGFB1 and IL10 expression by Tfr cells negatively associated with the expression of IFNG in tumor-infiltrating CD8 T cells. In an in vitro CD8 T cell/Tfr cell coculture system, we found that Tfr cells could significantly suppress the activation of CD8 T cells, in a manner that was dependent on IL-10 and probably on TGF-beta. Overall, our study found that Tfr cells could suppress CD8 T cells, and in ovarian cancer patients, the Tfr cells were increased in both frequency and function.