本文選題：肺癌 + 調(diào)節(jié)性T細(xì)胞　； 參考：《天津醫(yī)科大學(xué)》2016年碩士論文

【摘要】：目的:最近研究發(fā)現(xiàn)調(diào)節(jié)性T細(xì)胞(Regulatory T cells,Tregs)表面表達(dá)以糖蛋白A重復(fù)序列為主的蛋白(Glycoprotein A Repetitions Predominant,GARP),而且GARP被認(rèn)為是活化的Tregs特異性標(biāo)志分子。因此,我們研究GARP在肺癌患者來(lái)源Tregs中的表達(dá)情況,并分析其表達(dá)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(yīng)用流式細(xì)胞術(shù)檢測(cè)GARP在Tregs及傳統(tǒng)T細(xì)胞(Conventional T cells,Tconvs)的表達(dá)情況。比較肺癌組織和外周血Tregs和GARP+Tregs細(xì)胞的比例,分析Tregs和GARP+Tregs比例與患者臨床病理特征的關(guān)系。肺癌病人外周血Tregs和腫瘤細(xì)胞直接接觸共培養(yǎng)和Transwell共培養(yǎng)后,檢測(cè)腫瘤細(xì)胞對(duì)Tregs表面GARP表達(dá)水平的影響,進(jìn)一步檢測(cè)肺癌細(xì)胞培養(yǎng)上清對(duì)Tregs細(xì)胞GARP表達(dá)的影響。結(jié)果:GARP在肺癌組織Tregs中的表達(dá)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(wú)淋巴結(jié)轉(zhuǎn)移患者高于有淋巴結(jié)轉(zhuǎn)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(xì)胞系A(chǔ)549、H520、H460、LTEP-A-2和GLC-82均能誘導(dǎo)Tregs表面表達(dá)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(xì)胞誘導(dǎo)Tregs表面GARP的表達(dá)能力相近。A459和H520細(xì)胞培養(yǎng)上清仍能誘導(dǎo)Tregs表達(dá)GARP,進(jìn)一步表明腫瘤細(xì)胞可能通過(guò)分泌細(xì)胞因子促進(jìn)GARP表達(dá)。結(jié)論:GARP在肺癌組織Tregs中的表達(dá)升高,其表達(dá)與淋巴結(jié)轉(zhuǎn)移和臨床分期相關(guān)。腫瘤細(xì)胞促進(jìn)Tregs表面表達(dá)GARP的可能機(jī)制之一是分泌細(xì)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(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類(lèi)號(hào)】：R734.2

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