Interaction of cancer cell-derived Foxp3 and tumor microenvironment in human tongue squamous cell carcinoma
Interaction of cancer cell-derived Foxp3 and tumor microenvironment in human tongue squamous cell carcinoma
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人舌鳞状细胞癌中癌细胞来源的 Foxp3 与肿瘤微环境的相互作用
DOI：
10.1016/j.yexcr.2018.07.029
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发表时间：
2018-09-15
影响因子：
3.7
通讯作者：
Liang, Yu-jie
中科院分区：
文献类型：
--
作者：
Li, Kan;Huang, Si-hui;Liang, Yu-jie
叉头转录因子Foxp3已被证明对调节性T细胞(Treg)的分化和激活是必不可少的。近年来，Foxp3在肿瘤细胞(癌细胞来源的Foxp3)中的表达受到越来越多的关注，但其功能尚未得到证实。在本研究中，我们通过多种体外方法鉴定了癌细胞来源的Foxp3与舌鳞状细胞癌(TSCC)中肿瘤微环境的相互作用。我们用免疫组织化学方法检测到癌细胞来源的Foxp3与TSCC病变中Foxp3+淋巴细胞的浸润密切相关。Foxp3在TSCC中的表达调节了PBMC细胞因子(干扰素-γ、转化生长因子β、IL-2、IL-6、IL-1β、IL-10、IL-8、IL-17、IL-23)的分泌和CD4+T细胞的分化。作为反馈，增加转化生长因子β和减少IL-17进一步上调癌细胞衍生的Foxp3。此外，芯片上分析显示，转化生长因子β和IL-17均可降低TSCC中Foxp3结合基因的数量。GO和通路分析表明，经转化生长因子β或Th17处理后，Foxp3结合基因倾向于负调控转化生长因子β信号通路。综上所述，这项研究表明，癌细胞来源的Foxp3在TSCC微环境中以正反馈和负反馈促进Tregs的扩张。
The forkhead transcription factor, Foxp3, has been proved essential for differentiation and activation of regulatory T cells (Tregs). Recently, Foxp3 expression in tumor cells (cancer cell-derived Foxp3) has gained increasing interest, but the function has yet to be confirmed. In the current investigation, we identified the interaction of cancer cell-derived Foxp3 and tumor microenvironment in human tongue squamous cell carcinoma (TSCC) by various in vitro methods. We detected cancer cell-derived Foxp3 was closely associated with the infiltration of Foxp3 + lymphocytes in TSCC lesions using immunohistochemical staining. The cytokines secretion (IFN-gamma, TGF beta, IL-2, IL-6, IL-1 beta, IL-10, IL-8, IL-17, IL-23) of PBMC and differentiation of CD4 + T cells were modulated by the expression of Foxp3 in TSCC, shown by ELISA and flow cytometry. As feedback, increasing TGF beta and decreasing IL-17 further up-regulated cancer cell-derived Foxp3. Furthermore, CHIP on chip assay showed that both TGF beta and IL-17 decreased the number of Foxp3-binding genes in TSCC. GO and pathway analysis suggested that, treated with TGF beta or Th17, Foxp3-binding genes were inclined to the negative regulation of TGF beta signal pathway. Taken together, this study showed cancer cell-derived Foxp3 contributed to Tregs expansion in TSCC microenvironment with positive and negative feedbacks.