Increased prevalence of regulatory T cells in the lung cancer microenvironment: a role of thymic stromal lymphopoietin
Increased prevalence of regulatory T cells in the lung cancer microenvironment: a role of thymic stromal lymphopoietin
复制标题
肺癌微环境中调节性 T 细胞的患病率增加：胸腺基质淋巴细胞生成素的作用
DOI：
10.1007/s00262-011-1059-6
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发表时间：
2011-11-01
影响因子：
5.8
通讯作者：
Ren, Xiubao
中科院分区：
文献类型：
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作者：
Li, Hui;Zhao, Hua;Ren, Xiubao
肿瘤微环境中CD4 + CD25 +调节性T细胞（Tregs）的扩增是癌细胞逃避宿主防御的机制之一。胸腺基质淋巴细胞生成素（TSLP）有助于胸腺中天然Tregs的产生。因此，本研究旨在探讨TSLP在肺癌微环境中Tregs增多中的作用。肿瘤组织中TSLP蛋白的表达率较良性病变和非癌肺组织显著升高。肿瘤微环境中Tregs的数量与肺癌中TSLP的表达相关。从肺癌患者外周血单个核细胞（PBMCs）诱导出树突状细胞（DCs），分为未刺激组（imDCs）、人TSLP刺激组（TSLP - DCs）和脂多糖刺激组（LPS - DCs）。TSLP - DCs表达中等水平的CD83以及高水平的CD86、CD11C和HLA - DR，呈现出未成熟DCs的特征。TSLP - DCs分泌低水平的白细胞介素 - 6（IL - 6）、白细胞介素 - 12（IL - 12）、白细胞介素 - 10（IL - 10）、肿瘤坏死因子 - α（TNF - α）和干扰素 - γ（IFN - γ），以及高水平的转化生长因子 - β（TGF - β）和巨噬细胞衍生趋化因子（MDC）。与TSLP - DCs共培养的CD4 + CD25 - T细胞中Tregs的百分比在统计学上高于LPS - DCs和imDCs组。Transwell实验表明，与imDCs相比，TSLP - DCs吸引CD4 + CD25 - Tregs迁移的能力增强。这些结果表明TSLP蛋白在肺肿瘤组织中表达，并与Tregs的数量相关。TSLP - DCs可诱导CD4 + CD25 - T细胞分化为CD4 + CD25 + foxp3 + T细胞以及促进CD4 + CD25 + T细胞的迁移。
Expansion of CD4+CD25+ regulatory T cells (Tregs) in tumor microenvironment was one of the mechanisms by which cancer cells escaped host defense. Thymic stromal lymphopoietin (TSLP) contributes to the generation of natural Tregs in thymus. Therefore, the purpose of this report was to investigate the role of TSLP in the increasing prevalence of Tregs in lung cancer microenvironment. The expression ratio of TSLP protein in tumor tissues was significantly increased compared with that in benign lesion and non-cancer lung tissue. The prevalence of Tregs in tumor microenvironment was correlated with the expression of TSLP in lung cancer. Dendritic cells (DCs) were induced from peripheral blood mononuclear cells (PBMCs) collected from lung cancer patients and left unstimulated (imDCs) or exposed to hTSLP (TSLP-DCs) or LPS (LPS-DCs). TSLP-DCs expressed intermediate levels of CD83 and high levels of CD86, CD11C, and HLA-DR, which showed a characteristic of less mature DCs. TSLP-DCs secreted low levels of IL-6, IL-12, IL-10, TNF-alpha and IFN-gamma, and high levels of TGF-beta and MDC. The percentage of Tregs in CD4+CD25- T cells cocultured with TSLP-DCs group was statistically higher than that of LPS-DCs and imDCs. Transwell assays showed that TSLP-DCs exhibited increased ability to attract the migration of CD4+CD25- Tregs, when compared with imDCs. These results indicated that TSLP proteins were expressed in lung tumor tissue and correlated with the prevalence of Tregs. TSLP-DCs could induce CD4+CD25- T cells to differentiate into CD4+CD25+foxp3+ T cells and the migration of CD4+CD25+ T cells.