肿瘤患者中高表达人白细胞分化抗原25的调节T细胞检测及其临床意义

CD4^+CD25^(high) regulatory cells in peripheral blood of cancer patients

目的探讨肿瘤患者外周血高表达人白细胞分化抗原(CD)25的CD4+调节T细胞(CD4+CD25highTr)比率变化特点及其临床意义。方法用流式细胞术检测62例肿瘤患者外周血CD4+CD25high调节T细胞水平,并分层分析。结果62例肿瘤患者外周血中CD25highTr细胞占CD4+T细胞的百分比率(4·2%±1·9%)明显高于15名健康体检者(2·0%±1·0%,P<0·001);CD4+CD25highTr细胞且具有调节性T细胞的表面标记特征,即CD45-RA(-),CD69(-)。随疾病进展外周血D25highT细胞占CD4+T细胞百分比率逐渐升高,15例恶性肿瘤Ⅰ+Ⅱ期患者外周血D25highT细胞占CD4+T细胞的百分比率(2·4%±0·6%)与健康体检者比,差异无统计学意义(P>0·05)。21例Ⅲ期(3·5%±1·5%)、26例Ⅳ期(4·9%±1·7%)患者外周血D25highT细胞占CD4+T细胞的百分比率显著升高,与健康体检者比,差异有统计学意义(P<0·001)。Ⅰ、Ⅱ期与Ⅲ期比较,Ⅲ期与Ⅳ期比较,差异均有统计学意义(P<0·05,P<0·01)。提示外周血CD4+CD25highTr细胞比率高者预后较差。结论肿瘤患者外周血CD4+CD25highTr细胞水平明显升高,与肿瘤免疫功能低下及肿瘤发生发展密切相关。监测外周血CD4+CD25highTr细胞比率可评价肿瘤患者预后。

Objective To investigate the identification of a CD4^＋ population of regulatory T（Tr） cells in the circulation of humans expressing high levels of CD25 （ CD4^＋ CD25^hish ） that exhibit in vitro characteristics identical with those of the CD4^ ＋ CD25 ^＋ regulatory cells isolated in mice and to providing the opportunity for determining whether cancer patients exhibit an expanded CD4 ^＋ CD25^high pool. Methods The frequency of CD4^＋ CD25^high Tr cells in the peripheral blood of 62 cancer patients and 15 healthy controls was determined by flow cytometry. Results Compared with healthy control （ 2. 0% ± 1.0%, n = 15 ） , The frequency of CD4 ^＋ CD25^high in the peripheral blood of cancer patients was increased in the peripheral blood （4. 2% ± 1.9% ： n = 62, P 〈 0.001 ）. Comparing with healthy controls, 15 early stages cancer patients （ stage Ⅰ ＋ Ⅱ,2.4% ± 0. 6% ） didn＇t show a significant difference （ P 〉 0. 05 ）. The proportion of CD4^＋ CD25^high Tr cells in cancer patients with advanced stage（ stage Ⅲ.3.5% ±1.5%, n = 21, stageiv ：4. 9% ± 1.7%, n = 26）was significantly higher than those in healthy controls （P 〈 0. 001 ）. Furthermore, the proportion of the CD4 ^＋ CD25^high Tr cells in the peripheral blood in stage Ⅲ was higher than that in stage Ⅰ ＋ Ⅱ （ P 〈 0.05 ） , the proportion of the CD4^＋ CD25^high Tr cells in the peripheral blood in stage IV was higher than that in stage Ⅲ （ P 〈 0.01 ）. The phenotic chacteristics of the CD4^＋ CD25^high Tr cells were low expression of CD45RA and lacked markers of recent activation （CD69）. Indicating that patients, those with higher percentages of CD4^＋ CD25^high Tr cells had the poor prognosis. Conclusion There is an increased pool of CD4^＋ CD25^high in the peripheral blood of cancer patients. The relative increase in CD4 ^＋ CD25^high Tr cells may be related to immunosuppression and tumor progress in cancer patients. These results demonstrate the role of CD4^＋ CD25^high Tr cells in tumor-induced immune tolerance and the interest of Tr cells depletion to sensitize tumors to immunotherapy. It may be positive for prognosis analysis to montor proportion of CD4 ^＋ CD25^high Tr cells in the peripheral blood of cancer patient.