Enrichment of CCR6+Foxp3+ regulatory T cells in the tumor mass correlates with impaired CD8+ T cell function and poor prognosis of breast cancer
Enrichment of CCR6+Foxp3+ regulatory T cells in the tumor mass correlates with impaired CD8+ T cell function and poor prognosis of breast cancer
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DOI：
10.1016/j.clim.2010.01.014
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发表时间：
2010-06-01
影响因子：
8.6
通讯作者：
Xiong, Sidong
中科院分区：
文献类型：
--
作者：
Xu, Lin;Xu, Wei;Xiong, Sidong
CCR 6（+）亚群CD 4（+）调节性T细胞是新近发现的一类具有局部免疫抑制作用的T细胞亚群。然而，CCR 6（+）TcR是否存在于肿瘤环境中及其与肿瘤预后的关系仍有待进一步研究。在这项研究中，我们发现CCR 6（+）CD 4（+）CD 25（高）T细胞，表达高水平的CD 45 RO，主要富集在乳腺癌患者的肿瘤肿块。此外，在肿瘤进展过程中，患者肿瘤浸润淋巴细胞（TIL）中CCR 6（+）T细胞的频率显著增加，而不是CCR 6 T细胞的频率，这与TIL中IFN-γ（+）CD 8（+）T细胞的频率降低相关。最重要的是，CCR 6（+）TcR的频率与乳腺癌患者的生存率相关，而CCR 6（-）TcR的频率与乳腺癌患者的生存率无关。本研究提示，乳腺癌中一个新的肿瘤驻留TCR 6（+）TCR 7亚群可能是肿瘤免疫抑制的主要原因，也可能是乳腺癌预后不良的潜在预测因子。(C)2010年爱思唯尔公司All rights reserved.
CCR6(+) subset of CD4(+) regulatory T cells, a newly characterized subset of Tregs, has been reported to contribute to local immune inhibition. However, whether CCR6(+) Tregs are present in tumor environment and their relation to the prognosis of tumor remain to be elucidated. In this study, we found that CCR6(+) CD4(+) CD25(high) Tregs, expressing high levels of CD45RO, are dominantly enriched in tumor mass from patients with breast cancer. Furthermore, the frequency of CCR6(+) Tregs, but not CCR6 Tregs in tumor infiltrating lymphocytes (TILs), significantly increased in patients during tumor progression, which reversely correlated with decreased frequency of the IFN-gamma(+)CD8(+)T cells in TILs. Most importantly, the frequency of CCR6(+) Tregs, but not CCR6(-) Tregs, reversely correlated to the survival of patients with breast cancer. This study suggested that a new subset of tumor-resident Tregs, CCR6(+) Tregs, may be dominantly responsible for the immunosuppression in tumor immunity and a potential predictor of the poor prognosis of breast cancer. (C) 2010 Elsevier Inc. All rights reserved.