Department of Oncology, The Second People's Hospital of Yibin, Yibin, People's Republic of China.
Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
Cancer Med. 2023 Feb;12(4):4993-5008. doi: 10.1002/cam4.5194. Epub 2022 Oct 13.
Regulatory T cells (Tregs) have an important role in accelerating the immunosuppression of tumor. Tregs regulation is a hopeful strategy to improve the dismal prognosis of Esophageal cancer (EC), while its mechanisms have not yet been fully clarified.
To characterize the role of Tregs in EC, we comprehensively explored its prognostic value, clinical pathology partnership, related biological functions and potential mechanisms at transcriptome level. Through the integrated analysis of GEO and TCGA datasets, we comprehensively evaluated the Tregs infiltration patterns in EC patients. The correlation between Tregs infiltration and genomic characteristics, as well as biological functions were analyzed by a variety of computational algorithms.
We observed that Tregs were significantly upregulated in EC and involved in various immune processes. According to TCGA and GEO transcriptional classification schemes, Tregs specific genes were observed to be highly expressed in tumor samples, as well as were closely associated with poor prognosis and worse clinical outcomes. In addition, EC patients can be stratified into high-risk and low-risk immune subgroups according to Tregs/macrophages infiltration level, and the results showed significant differences in tumor development, biological processes and probe gene expression pattern. The multi-variate analysis revealed that the interaction between STAT3 and Foxp3 was a potential prognostic signature of Tregs in EC, especially the modulation effect of STAT3 on Foxp3 expression, which has not been well studied in EC. We also identified that STAT3 and Foxp3 expression presented a high accuracy in predicting Tregs infiltration level in EC patients (AUC: 0.817; 95% CI: 0.756-0.878).
Our results revealed that Tregs have the potential to predict prognosis and tumor deterioration in EC patients. A comprehensive landscape of Tregs regulation mechanisms will help us interpret the immunosuppression of tumor microenvironment (TME) and novel strategies for EC immunotherapy.
调节性 T 细胞（Tregs）在加速肿瘤免疫抑制方面具有重要作用。Tregs 调节是改善食管癌（EC）预后不佳的有希望的策略，但其机制尚未完全阐明。
为了研究 Tregs 在 EC 中的作用，我们从转录组水平全面探讨了其预后价值、临床病理关系、相关生物学功能和潜在机制。通过综合分析 GEO 和 TCGA 数据集，我们全面评估了 EC 患者中 Tregs 浸润模式。通过各种计算算法分析了 Tregs 浸润与基因组特征和生物学功能的相关性。
我们观察到 Tregs 在 EC 中显著上调，并参与了各种免疫过程。根据 TCGA 和 GEO 转录分类方案，Tregs 特异性基因在肿瘤样本中表达较高，并且与不良预后和较差的临床结局密切相关。此外，根据 Tregs/巨噬细胞浸润水平，EC 患者可分为高危和低危免疫亚组，结果显示肿瘤发展、生物过程和探针基因表达模式存在显著差异。多变量分析显示，STAT3 和 Foxp3 的相互作用是 EC 中 Tregs 的潜在预后标志物，特别是 STAT3 对 Foxp3 表达的调节作用，在 EC 中尚未得到很好的研究。我们还发现，STAT3 和 Foxp3 的表达在预测 EC 患者 Tregs 浸润水平方面具有较高的准确性（AUC：0.817；95%CI：0.756-0.878）。
我们的研究结果表明，Tregs 有可能预测 EC 患者的预后和肿瘤恶化。全面了解 Tregs 调节机制有助于我们解释肿瘤微环境（TME）的免疫抑制作用，并为 EC 免疫治疗提供新的策略。
