本文選題：肺癌 + 調節(jié)性T細胞　； 參考：《天津醫(yī)科大學》2016年碩士論文

【摘要】：目的:最近研究發(fā)現(xiàn)調節(jié)性T細胞(Regulatory T cells,Tregs)表面表達以糖蛋白A重復序列為主的蛋白(Glycoprotein A Repetitions Predominant,GARP),而且GARP被認為是活化的Tregs特異性標志分子。因此,我們研究GARP在肺癌患者來源Tregs中的表達情況,并分析其表達的臨床意義。方法:收集39例肺癌組織和50例肺癌病人外周血,應用流式細胞術檢測GARP在Tregs及傳統(tǒng)T細胞(Conventional T cells,Tconvs)的表達情況。比較肺癌組織和外周血Tregs和GARP+Tregs細胞的比例,分析Tregs和GARP+Tregs比例與患者臨床病理特征的關系。肺癌病人外周血Tregs和腫瘤細胞直接接觸共培養(yǎng)和Transwell共培養(yǎng)后,檢測腫瘤細胞對Tregs表面GARP表達水平的影響,進一步檢測肺癌細胞培養(yǎng)上清對Tregs細胞GARP表達的影響。結果:GARP在肺癌組織Tregs中的表達明顯高于Tconvs(P0.0001)。肺癌組織Tregs的比例高于外周血(P=0.0032),肺癌組織中GARP+Tregs的比例也顯著高于外周血(P0.0001)。肺癌組織中GARP+Tregs的比例在無淋巴結轉移患者高于有淋巴結轉移患者(P=0.0221),I期和II期患者高于III期和IV期患者(P=0.0005)。人肺癌細胞系A549、H520、H460、LTEP-A-2和GLC-82均能誘導Tregs表面表達GARP,其中A459和H520共培養(yǎng)組GARP+Tregs比例高于其它組。在Transwell共培養(yǎng)組與直接接觸共培養(yǎng)組,A459和H520細胞誘導Tregs表面GARP的表達能力相近。A459和H520細胞培養(yǎng)上清仍能誘導Tregs表達GARP,進一步表明腫瘤細胞可能通過分泌細胞因子促進GARP表達。結論:GARP在肺癌組織Tregs中的表達升高,其表達與淋巴結轉移和臨床分期相關。腫瘤細胞促進Tregs表面表達GARP的可能機制之一是分泌細胞因子。
[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.
【學位授予單位】：天津醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2016
【分類號】：R734.2

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