Expression of TNFR2 by regulatory T cells in peripheral blood is correlated with clinical pathology of lung cancer patients
Expression of TNFR2 by regulatory T cells in peripheral blood is correlated with clinical pathology of lung cancer patients
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DOI：
10.1007/s00262-015-1751-z
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发表时间：
2015-08
期刊：
影响因子：
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通讯作者：
Fan Yan;R. Du;F. Wei;Hua Zhao;Jinpu Yu;Chang-li Wang;Z. Zhan;T. Ding;X. Ren;Xin Chen;Hui Li
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文献类型：
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作者：
Fan Yan;R. Du;F. Wei;Hua Zhao;Jinpu Yu;Chang-li Wang;Z. Zhan;T. Ding;X. Ren;Xin Chen;Hui Li
CD 4 + FoxP 3+调节性T细胞（TCRs）代表癌症免疫逃避的主要细胞介质。据报道，在小鼠和人类中，TcG上肿瘤坏死因子受体II型（TNFR 2）的表达鉴定了最大抑制性Treg群体。因此，我们研究了43例肺癌患者外周血（PB）中存在的TNFR 2 + T细胞的表型和功能。进一步分析了Treg上TNFR 2表达与临床病理因素的相关性。结果显示，在肺癌患者的PB中，Tcells表达的TNFR 2水平明显高于常规T细胞（Tconvs）。TNFR 2的表达似乎比CD 25+和CD 127-与FoxP 3表达更相关。肺癌患者中的PB TNFR 2 + T细胞增殖性更强，表达更高水平的免疫抑制分子CTLA-4，因此更有效地抑制共培养的CD 8 CTL产生IFNγ。更重要的是，TNFR 2在TcB上的高表达水平与肺癌患者的淋巴浸润、远处转移和更晚期的临床分期相关。因此，我们的研究表明，TNFR 2 + T细胞在促进肿瘤的进行性转移中起作用，并且PB T细胞表达TNFR 2可能被证明是肺癌患者的有用的预后标志物。
CD4+FoxP3+regulatory T cells (Tregs) represent a major cellular mediator of cancer immune evasion. The expression of tumor necrosis factor receptor type II (TNFR2) on Tregs is reported to identify the maximally suppressive Treg population in both mice and human. We therefore investigated the phenotype and function of TNFR2+Tregs present in the peripheral blood (PB) of 43 lung cancer patients. Further, the association of TNFR2 expression on Tregs with clinicopathological factors was analyzed. The results showed that in the PB of lung cancer patients, Tregs expressed markedly higher levels of TNFR2 than conventional T cells (Tconvs). Expression of TNFR2 appeared to correlate better than CD25+and CD127−with FoxP3 expression. PB TNFR2+Tregs in lung cancer patients were more proliferative and expressed higher levels of the immunosuppressive molecule CTLA-4, and consequently more potently suppressed IFNγ production by cocultured CD8 CTLs. More importantly, higher TNFR2 expression levels on Tregs were associated with lymphatic invasion, distant metastasis and more advanced clinical stage of lung cancer patients. Therefore, our study suggests that TNFR2+Tregs play a role in promoting tumor progressive metastasis and expression of TNFR2 by PB Tregs may prove to be a useful prognostic marker in lung cancer patients.