The crosstalk: Tumor-infiltrating lymphocytes rich in regulatory T cells suppressed cancer-associated fibroblasts.
The crosstalk: Tumor-infiltrating lymphocytes rich in regulatory T cells suppressed cancer-associated fibroblasts.
复制标题
串扰：富含调节性 T 细胞的肿瘤浸润淋巴细胞抑制了癌症相关成纤维细胞。
DOI：
10.3109/0284186x.2012.760847
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发表时间：
2013-11
期刊：
影响因子：
--
通讯作者：
Zheng S
中科院分区：
文献类型：
--
作者：
Fu Z;Zuo Y;Li D;Xu W;Li D;Chen H;Zheng S
癌相关成纤维细胞（CAF）与癌细胞或肿瘤浸润淋巴细胞（TIL）与癌细胞之间的相互作用在癌症的进展和转移中起重要作用。然而，有关肿瘤微环境（TME）中CAFs和TIL之间串扰的研究仍然缺乏。在本研究中，我们主要研究了CAFs和TILs之间的相互作用。使用苏木精-伊红染色和抗CD 3、抗Foxp 3和抗α-平滑肌肌动蛋白抗体的免疫组化评价乳腺癌组织中富含调节性T细胞（TCLs）的TIL的分布。采用免疫细胞化学和流式细胞术对体外培养的人CAFs/正常成纤维细胞（NF）和TIL进行鉴定和检测。这些细胞类型之间的直接相互作用，研究通过析因设计在共培养系统。使用Transwell平板测定它们的间接相互作用。碘化丙啶染色分析与TIL共培养的CAFs/NFs的细胞周期和凋亡。组织化学结果显示，包括TIF在内的TILs主要分布于癌间质中，与CAFs相邻。这一发现意味着这两种细胞类型在TME中密切相互作用。对培养细胞的鉴定表明，CAF在体外有限的传代内保持其活化的表型，并且TIL群体含有高百分比的Tcl 3。析因设计的数据分析表明，在直接和间接接触方式中，CAF、NF和TILs之间存在显著的相互作用。TILs对CAFs和NF有明显的抑制作用，这可能是由TILs或TCFs分泌的细胞因子诱导的。CAFs/NFs中未检测到凋亡，但细胞周期分析表明，TILs及其分泌的细胞因子将CAFs/NFs阻滞在G2/M期。CAF和NF被富含Tregs的TIL显著抑制。这表明TIL和CAF之间的相互作用可能以未知的方式改变TME。
The interactions between cancer-associated fibroblasts (CAFs) and cancer cells or tumor-infiltrating lymphocytes (TILs) and cancer cells play important roles in cancer progression and metastasis. However, studies related to the crosstalk between CAFs and TILs in tumor microenvironment (TME) are still lacking. In this study, we mainly investigated the interactions between CAFs and TILs. The distribution of TILs rich in regulatory T cells (Tregs) in breast cancer tissues was evaluated using hematoxylin-eosin staining and immunohistochemistry with anti-CD3, anti-Foxp3, and anti-α-smooth muscle actin antibodies. Homologous CAFs/normal fibroblasts (NFs) and TILs cultured in vitro were identified and detected using immunocytochemistry and flow cytometry (FCM). The direct interaction among these cell types was studied via a factorial design in a co-cultured system. Their indirect interaction was assayed using Transwell plates. The cell cycle and apoptosis of CAFs/NFs co-cultured with TILs was analyzed using propidium iodide staining. Histochemistry demonstrated most of the TILs including Tregs, were distributed in the cancer stroma, adjoining to CAFs. This finding implies that both cell types interact closely in the TME. Identification of the cultured cells showed that CAFs maintained their activated phenotype within limited passages in vitro, and that the TILs population contained a high percentage of Tregs. Data analysis of the factorial design suggests significant interactions among CAFs, NFs, and TILs in both direct and indirect contact ways. The CAFs and NFs were suppressed signally by TILs, which are probably induced by the secretory cytokines derived from TILs or Tregs. Although apoptosis was not detected in CAFs/NFs, the cell cycle assay suggested that the CAFs/NFs were arrested in the G2/M phase by the TILs and their secretory cytokines. CAFs and NFs were dramatically suppressed by Tregs-rich TILs. This suggests the interaction between TILs and CAFs might modify the TME in an unknown manner.