Dysregulation of helper T (Th) cell subsets has been contributed to the initiation and propagation of esophageal squamous cell carcinoma (ESCC). Different microRNAs (miRNAs) have been reported to control the development and functions of tumor-associated immune cells in ESCC. Here, we aimed to assess the IL-10, TGF-β, IFN-γ, and IL-17a-producing CD3+CD8- T cells in association whit miR-21, miR-29b, miR-106a, and miR-155 expression in ESCC patients. A total of 34 ESCC patients including 12 newly diagnosed (ND) and 22 under-treatment (UT) cases and also 34 age-matched healthy donors were enrolled. Flow cytometric characterization of stimulated T cells was performed by staining of the cells with fluorescent conjugated specific anti-human CD3 and CD8 cell surface markers as well as IL-17a, IFN-γ, IL-10, and TGF-β intracytoplasmic cytokines. Circulating RNA was extracted from the plasma, and qRT-PCR was used to evaluate the expression of microRNAs. TGF-β plasma levels were also assessed by ELISA. Results showed that the frequency of Th cells was significantly reduced in patients. A significant increase in Treg as well as Th17 cells population in both patient subgroups was observed. ND patients showed elevated level of Th1 cells and IL-10. However the mean expression of IFN-γ was significantly decreased in Th cells. We also detected higher level of miR-21 in the ESCC patients which was significantly correlated with different subsets of Th cells. Our findings revealed that immune response related to the Th cells is highly impaired in ESCC patients. Association between miR-21 and Th subsets could be correlated with the impairment of anti-tumor immunity and ESCC pathogenesis, which could be potentially used as an important target for immunotherapeutic approaches.

中文翻译：

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食管鳞状细胞癌（ESCC）患者的辅助性T淋巴细胞功能异常与miR-21异常产生高度相关。

辅助T（Th）细胞亚群的失调已导致食管鳞状细胞癌（ESCC）的发生和传播。据报道，不同的microRNA（miRNA）可控制ESCC中与肿瘤相关的免疫细胞的发育和功能。在这里，我们旨在评估与miR-21，miR-29b，miR-106a和miR-155相关的产生IL-10，TGF-β，IFN-γ和IL-17a的CD3 + CD8-T细胞在ESCC患者中的表达。共有34例ESCC患者入组，包括12例新诊断（ND）和22例治疗不足（UT）病例，以及34例年龄匹配的健康捐献者。通过用荧光偶联的特异性抗人CD3和CD8细胞表面标志物以及IL-17a，IFN-γ，IL-10和TGF-β胞浆内细胞因子对细胞进行染色，对受刺激的T细胞进行流式细胞仪表征。从血浆中提取循环RNA，并使用qRT-PCR评估microRNA的表达。还通过ELISA评估了TGF-β血浆水平。结果表明，患者中Th细胞的频率显着降低。在两个患者亚组中均观察到Treg和Th17细胞群体的显着增加。ND患者显示Th1细胞和IL-10水平升高。然而，Th细胞中IFN-γ的平均表达显着降低。我们还在ESCC患者中检测到更高水平的miR-21，这与Th细胞的不同亚群显着相关。我们的发现表明，ESCC患者与Th细胞相关的免疫反应受到极大损害。miR-21和Th亚群之间的关联可能与抗肿瘤免疫功能受损和ESCC发病机制有关，