[摘要] 目的：探讨Tim-3 在食管癌患者T细胞表面的表达及其临床意义。方法：收集2016 年9 月至2018 年4 月郑州大学第一附属医院胸外科25 例食管癌患者的新鲜肿瘤组织和癌旁组织及配对的外周静脉血，同时取10 例健康人外周静脉血。流式细胞术检测25 例食管癌患者癌组织及外周血单个核细胞（peripheral blood mononuclear cell, PBMC）中T细胞Tim-3、早期凋亡分子和内因子的表达水平，并分析了Tim-3+T细胞的比例与临床病理参数的关系。qPCR检测肿瘤组织及癌旁组织中Tim-3 的表达水平。运用TCGA数据库进一步验证Tim-3 在肿瘤组织和癌旁组织中的表达水平及其与预后的关系。结果：结果发现Tim-3 在食管癌患者肿瘤组织T细胞表达水平较高（P<0.01）。Tim-3+T细胞功能呈耗竭状态（P<0.05 或P<0.01），且食管癌微环境中T细胞表面Tim-3 的表达与淋巴结转移和临床分期密切相关（均P<0.01）。结论：Tim-3 在食管癌患者T细胞表面的表达导致T细胞功能耗竭，提示Tim-3 可能成为一个潜在的食管癌治疗靶点。

[Abstract] Objective: To investigate the expression of Tim-3 on the surface of T cells in patients with esophageal cancer, and to explore its clinical significance. Methods: Fresh tumor tissues, paracancerous tissues, and peripheral blood were collected from 25 patients with esophageal cancer at the first affiliated Hospital of Zhengzhou University from September 2016 to April 2018. Peripheral blood from 10 healthy subjects was also collected during the same time period. The expressions of Tim-3, early apoptotic molecules and intrinsic factors in tumor tissues and peripheral blood PBMCs of 25 esophageal cancer patients were determined by flow cytometry.Also, the correlation between Tim-3+ T cell proportion and pathological parameters was investigated. The expression of Tim-3 in tumor tissues and paracancerous tissues was detected by fluorescence quantitative real-time polymerase chain reaction (qPCR). TCGA database was used to further verify the expression of Tim-3 in tumor tissues and paracancerous tissues, as well as its relationship with prognosis. Results: Tim-3 expression on T cells was higher in tumor tissues from esophageal cancer patients (P<0.01). Tim-3+T cell function was in an exhausted status(P<0.05 or P<0.01), and the expression of Tim-3 on the surface of T cells in esophageal cancer microenvironment was closely related to lymph node metastasis and clinical staging (all P<0.01). Conclusion: Taken together, Tim-3 expression on the surface of T cells could induce T cell dysfunction in patients with esophageal cancer, suggesting that Tim-3 may serve as a potential therapeutic target for esophageal cancer.

国家自然科学基金资助项目（No.81773045）；河南省医学科技攻关计划资助项目（No.201702005）