结肠癌患者外周血γδT细胞Tim-3、PD-1表达及其临床意义  

Expressions and Clinical Significance of Tim-3 and PD-1 on Peripheral Blood γδ T Cells in Patients With Colon Cancer

作　　者：李晓咪 陆慧敏 李歌 石通国 张光波 陈卫昌[1,2,3] LI Xiaomi;LU Huimin;LI Ge;SHI Tongguo;ZHANG Guangbo;CHEN Weichang(Department of Gastroenterology,the First Affiliated Hospital of Soochow University,Suzhou,Jiangsu Province 215006;Jiangsu Key Laboratory of Gastrointestinal Tumor Immunology,Suzhou,Jiangsu Province;Jiangsu Key Laboratory of Clinical Immunology,Suzhou,Jiangsu Province)

机构地区：[1]苏州大学附属第一医院消化内科,215006 [2]江苏省(科教强卫)胃肠道肿瘤免疫重点实验室 [3]江苏省(高校)临床免疫学重点实验室

出　　处：《胃肠病学》2019年第3期134-138,共5页Chinese Journal of Gastroenterology

基　　金：国家自然科学基金(81672372)

摘　　要：背景:肿瘤的发生与免疫系统功能密切相关,共刺激分子异常表达与执行固有免疫功能的γδT细胞功能异常有关。T细胞免疫球蛋白和黏蛋白分子-3(Tim-3)和程序性死亡分子-1(PD-1)是重要的负性共刺激分子,与相应配体结合后可影响T淋巴细胞免疫功能,从而介导肿瘤细胞免疫逃逸。目的:初步探讨结肠癌患者外周血γδT细胞表面Tim-3、PD-1表达及其临床意义。方法:选取2017年12月—2018年6月苏州大学附属第一医院44例住院结肠癌患者,采集术前外周血标本,40名健康志愿者作为对照组,以密度梯度离心法分离外周血单个核细胞(PBMC),流式细胞术检测γδT细胞表面Tim-3、PD-1表达,分析两者表达与结肠癌临床病理特征的相关性。结果:结肠癌患者外周血Tim-3^+、PD-1^+、Tim-3^+PD-1+γδT细胞比例均显著高于健康志愿者(P <0. 05),并与肿瘤体积和TNM分析呈显著正相关(P <0. 05),与患者性别、年龄、肿瘤部位、有无远处转移则无明显相关性(P> 0. 05)。结论:结肠癌患者外周血γδT细胞表面Tim-3、PD-1表达明显升高并与肿瘤临床病理分期相关,有可能成为评估结肠癌发生、发展的客观指标。Background:The occurrence of tumor is closely related to the function of immune system.As an effector cell of innate immunity,the function ofγδT cells is reported to be regulated by co-stimulatory molecules.T-cell immunoglobulin mucin-3(Tim-3)and programmed death-1(PD-1),two critical inhibitory co-stimulatory molecules,may affect the immune function of T lymphocytes via binding with their ligands,thus mediating the immune escape of tumor cells.Aims:To investigate the expressions and clinical significance of Tim-3 and PD-1 onγδT cells in peripheral blood of colon cancer patients.Methods:Peripheral blood samples of 44 colon cancer patients were collected preoperatively at the First Affiliated Hospital of Soochow University from Dec.2017 to Jun.2018.Forty healthy volunteers were served as controls.The peripheral blood mononuclear cells(PBMCs)were isolated by density gradient centrifugation.Expressions of Tim-3 and PD-1 onγδT cells were detected by flow cytometry,and their correlations with tumor clinicopathological characteristics were analyzed.Results:The proportions of Tim-3^+,PD-1^+and Tim-3^+PD-1^+γδT cells in peripheral blood of colon cancer patients were significantly higher than those of healthy volunteers(P<0.05),and was positively correlated with the tumor volume and TNM staging(P<0.05).No correlations were found between proportions of Tim-3+,PD-1+and Tim-3+PD-1+γδT cells and the gender,age,tumor location and distant metastasis of colon cancer patients(P>0.05).Conclusions:Tim-3 and PD-1 are highly expressed onγδT cells in peripheral blood of colon cancer patients and associated with the clinicopathological stage of tumor.Expressions of Tim-3 and PD-1 on peripheral bloodγδT cells might be the promising objective indicators for evaluating the development and progression of colon cancer.

关 键 词：结肠肿瘤 T淋巴细胞 ΓΔT细胞 共刺激及抑制T细胞受体 T细胞免疫球蛋白和黏蛋白分子-3 程序性死亡分子-1 

分 类 号：R735.35[医药卫生—肿瘤]