肺癌患者CD4+CD25high Foxp3+调节性T细胞的格局变化及意义

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。

Changed proportion of CD4 + CD25highFoxp3 +T regulate cells and its significance in lung cancer patients

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 cells,was detected by real-time PCR.Results:Compared to the control,a decreased ratio of CD4~+ vs CD8~+T cells 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 cells is associated with the pathologic classification of lung cancer.Conclusion:The proportion of CD4~+CD25~(high)Foxp3~+Treg cells was increased in lung cancer patients,which consequently resulted in the inhibition of immune response and tumor development.