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肝癌细胞通过产生转化生长因子-β1诱导调节性T细胞并导致预后不良。

Hepatocellular Carcinoma Cells Induce Regulatory T Cells and Lead to Poor Prognosis via Production of Transforming Growth Factor-β1.

作者信息

Wang Yi, Liu Taotao, Tang Wenqing, Deng Bin, Chen Yanjie, Zhu Jimin, Shen Xizhong

机构信息

Department of Gastroenterology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China.

出版信息

Cell Physiol Biochem. 2016;38(1):306-18. doi: 10.1159/000438631. Epub 2016 Jan 25.

DOI:10.1159/000438631
PMID:26799063
Abstract

BACKGROUND/AIMS: Regulatory T cells (Tregs) are associated with a poor prognosis in hepatocellular carcinoma (HCC). The purpose of the study was to explore the mechanisms of Tregs accumulation in HCC.

METHODS

We analyzed the frequency of Tregs in HCC by flow cytometry and immunohistochemistry. We also established a transforming growth factor (TGF)-β1-knockdown cell line by lentivirus-mediated RNA interference. Mouse CD4+CD25- T cells were cultured in supernatants from various cell lines.

RESULTS

HCC patients had a high frequency of Tregs, and high numbers of Tregs correlated with a poor prognosis. Liver cancer cells induced Treg production by secreting TGF-β1. In vivo experiments indicated that knockdown of TGF-β1 reduced the numbers of Tregs and metastatic nodules in mice.

CONCLUSIONS

These results indicate that cancer-secreted TGF-β1 may increase Tregs, and TGF-β1 knockdown might impair immunosuppression in the tumor microenvironment by decrease Tregs.

摘要

背景/目的:调节性T细胞(Tregs)与肝细胞癌(HCC)的不良预后相关。本研究旨在探讨Tregs在HCC中积聚的机制。

方法

我们通过流式细胞术和免疫组织化学分析了HCC中Tregs的频率。我们还通过慢病毒介导的RNA干扰建立了转化生长因子(TGF)-β1敲低细胞系。将小鼠CD4+CD25-T细胞培养在各种细胞系的上清液中。

结果

HCC患者的Tregs频率较高,大量Tregs与不良预后相关。肝癌细胞通过分泌TGF-β1诱导Treg产生。体内实验表明,敲低TGF-β1可减少小鼠体内Tregs的数量和转移结节。

结论

这些结果表明,癌症分泌的TGF-β1可能增加Tregs,而敲低TGF-β1可能通过减少Tregs来损害肿瘤微环境中的免疫抑制作用。

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