目的:研究肺癌患者外周血(PBMC)及肿瘤浸润淋巴细胞(TIL)中CD4^+ CD25^high Foxp3^+调节性T细胞(Treg)的比例改变,探讨其在抗肿瘤免疫中的调节作用。方法:分离肺癌患者PBMC及TIL,FACS分析CD4^+/CD8^+T细胞的比值及CD4^+ CD25^highT细胞占CD4^+T细胞的比例。Real-time PCR检测Treg特异性转录因子Foxp3基因在PBMC及TIL中的表达。结果:肺癌患者PBMC及TIL中CD4^+/CD8^+比值降低;而CD4^+ CD25^high T细胞在CD4^+T细胞中所占比例升高;Foxp3基因仅在TIL中高表达,而在PBMC中低或不表达,表明肿瘤局部的CD4^+ CD25^high T细胞主要是CD4^+ CD25^high Foxp3^+ Treg。结合临床资料分析显示Treg在肺腺癌比例较高。结论:CD4^+ CD25^high Foxp3^+ Treg在肺癌患者肿瘤浸润淋巴细胞中明显升高,可能与其通过细胞与细胞间接触抑制CD8^+T细胞的杀伤效应,最终发挥免疫抑制效应相关。
Objective:To study whether the change of CD4^+ CD25^high Foxp3^+ Treg cells in lung cancer patients influences the immune response and is associated with the tumor development. Methods: Lymphocytes isolated from blood and tumor mass of lung cancer patients were analyzed for the ratio of CD4 ^+ vs CD8 ^+ T cells and the proportion of CD4^+ CD25^high T cells by flow cytometry, lymphocytes from health adults were served as control. The mRNA expression of Foxp3 which is the specific marker of T regular ceils, was detected by real-time PCR. Results: Compared to the control, a decreased ratio of CD4 ^+ vs CD8 ^+T ceils and an increased proportion of CD4 ^+ CD25^high T cells were observed in PBMC and tumor infiltrated lymphocytes(TILs) of lung cancer patient. However, the Foxp3 expression was greatly increased only in the TILs, indicating more CD4^+ CD25^high Foxp3 ^+Treg cells aggregated in the tumor mass. Combined with clinical information, data showed that enhanced proportion of CD4^+ CD25^high Foxp3 ^+ Treg ceils is associated with the pathologic classification of lung cancer. Conclusion:The proportion of CD4^+ CD25^high Foxp3 ^+ Treg ceils was increased in lung cancer patients, which consequently resulted in the inhibition of immune response and tumor development.