GARP在肺癌患者来源调节性T细胞中的表达及临床意义

发布时间：2018-04-27 20:35

本文选题：肺癌 + 调节性T细胞　；参考：《天津医科大学》2016年硕士论文

【摘要】：目的:最近研究发现调节性T细胞(Regulatory T cells,Tregs)表面表达以糖蛋白A重复序列为主的蛋白(Glycoprotein A Repetitions Predominant,GARP),而且GARP被认为是活化的Tregs特异性标志分子。因此,我们研究GARP在肺癌患者来源Tregs中的表达情况,并分析其表达的临床意义。方法:收集39例肺癌组织和50例肺癌病人外周血,应用流式细胞术检测GARP在Tregs及传统T细胞(Conventional T cells,Tconvs)的表达情况。比较肺癌组织和外周血Tregs和GARP+Tregs细胞的比例,分析Tregs和GARP+Tregs比例与患者临床病理特征的关系。肺癌病人外周血Tregs和肿瘤细胞直接接触共培养和Transwell共培养后,检测肿瘤细胞对Tregs表面GARP表达水平的影响,进一步检测肺癌细胞培养上清对Tregs细胞GARP表达的影响。结果:GARP在肺癌组织Tregs中的表达明显高于Tconvs(P0.0001)。肺癌组织Tregs的比例高于外周血(P=0.0032),肺癌组织中GARP+Tregs的比例也显著高于外周血(P0.0001)。肺癌组织中GARP+Tregs的比例在无淋巴结转移患者高于有淋巴结转移患者(P=0.0221),I期和II期患者高于III期和IV期患者(P=0.0005)。人肺癌细胞系A549、H520、H460、LTEP-A-2和GLC-82均能诱导Tregs表面表达GARP,其中A459和H520共培养组GARP+Tregs比例高于其它组。在Transwell共培养组与直接接触共培养组,A459和H520细胞诱导Tregs表面GARP的表达能力相近。A459和H520细胞培养上清仍能诱导Tregs表达GARP,进一步表明肿瘤细胞可能通过分泌细胞因子促进GARP表达。结论:GARP在肺癌组织Tregs中的表达升高,其表达与淋巴结转移和临床分期相关。肿瘤细胞促进Tregs表面表达GARP的可能机制之一是分泌细胞因子。
[Abstract]:Aim: to investigate the expression of Glycoprotein A Repetitions predominance Repetitions GARPN on regulatory T cells (Tregs) on the surface of regulatory T cells (Tregs). GARP is considered to be an activated Tregs specific marker. Therefore, we studied the expression of GARP in Tregs of lung cancer patients and analyzed its clinical significance. Methods: the expression of GARP in Tregs and conventional T cells was detected by flow cytometry in 39 cases of lung cancer and 50 cases of peripheral blood of lung cancer patients. The ratio of Tregs and GARP Tregs cells in lung cancer tissue and peripheral blood was compared, and the relationship between Tregs and GARP Tregs ratio and clinicopathological features was analyzed. After direct contact coculture of Tregs and tumor cells from peripheral blood of lung cancer patients and co-culture of Transwell, the effect of tumor cells on the expression of GARP on Tregs surface was detected, and the effect of supernatant of lung cancer cell culture on GARP expression of Tregs cells was further examined. Results the expression of Tregs in lung cancer was significantly higher than that in Tconvsberg P 0.0001. The percentage of Tregs in lung cancer tissue was higher than that in peripheral blood P0. 0032, and the proportion of GARP Tregs in lung cancer tissue was significantly higher than that in peripheral blood P0. 0001. The proportion of GARP Tregs in lung cancer was higher in patients without lymph node metastasis than in patients with stage I and II of lymph node metastasis than in patients with stage III and stage IV. Human lung cancer cell line A549H _ 520H _ 460 LTEP-A-2 and GLC-82 could induce the expression of GARP on the surface of Tregs. The ratio of GARP Tregs in A459 and H _ 520 co-culture group was higher than that in other groups. In Transwell co-culture group and direct contact co-culture group, the expression of GARP on Tregs surface was similar to that induced by A459 and H520 cells. The supernatants of A459 and H520 cells could still induce Tregs expression, which further indicated that tumor cells could promote GARP expression by secreting cytokines. Conclusion the expression of Tregs was increased in lung cancer tissues, and the expression was correlated with lymph node metastasis and clinical stage. One of the possible mechanisms of tumor cells promoting the expression of GARP on the surface of Tregs is the secretion of cytokines.
【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R734.2

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