CD4+CD25+调节性T细胞对晚期肺癌患者免疫抑制作用的研究

目的 探讨Treg及Th1/Th2类细胞因子在晚期肺癌肿瘤免疫抑制中的作用.方法 选取100例初治晚期肺癌患者及50例健康自愿者.采用流式细胞术检测其外周血中Treg、Th1类细胞因子(IFN-γ、IL-2、TNF-a)、Th2类细胞因子(IL-4、IL-6、IL-10)水平,同时分析CD4+CD25+Treg与Th1/Th2类细胞因子之间的相关性.结果 ①晚期肺癌患者外周血中Treg为(11.12±5.83)%,高于健康对照组(7.46±3.07)%,差异有统计学意义(P=0.003);②化疗前肺癌患者外周血中Treg为(11.12±5.83)%,明显高于化疗后(6.45±3.74)%,差异有统计学意义(P<0.001);③晚期肺癌患者与正常对照组Th1/Th2类细胞因子水平分别为:IFN-γ(8.56±3.62 vs 10.79±3.27,P=0.049)、IL-2(8.48±2.87 vs 10.22±4.03,P=0.03)、TNF-a(6.18±2.67vs8.14±2.87,P=0.007)、IFN-γ/IL-4(3.33±1.44 vs 4.09±1.00,P=0.028)、IL-4(3.17±1.19 vs 2.45±0.43,P<0.001)、IL-6(3.88±2.08 vs 2.33±0.88,P<0.001)、IL-10(3.64±1.73 vs 2.54±1.08,P=0.008),其中Th2类因子水平明显升高,差异有统计学意义(P均<0.05);④CD4+CD25+Treg与Th1类细胞因子IFN-γ、TNF-a、IL-2及IL-6无相关性(P均>0.05);与Th1/Th2(γ=-0.273,P=0.003)呈负相关;与Th2类细胞因子IL-4(γ=0.237,P=0.009)、IL-10(0.626,P<0.001)呈正相关(P均<0.05).结论 晚期肺癌患者CD4+CD25+Treg、Th2类细胞因子水平显著升高,Th1类细胞因子水平下降,它们共同导致肿瘤患者免疫抑制及肿瘤进展,监测其水平变化有助于判断肺癌患者疗效、预后,有效调控CD4+CD25+Treg及负性细胞因子水平可能是治疗肺癌的一个新策略.

Study of the Immunosuppressive Effect of CD4 +CD25 +Regulatory T Cells on Patients with Advanced Lung Cancer

Objective To explore the role of CD 4 +CD25 +regulatory T cells and Th 1 and Th2 cytokines in tumor immu-nosuppression of advanced lung cancer patients .Methods The blood samples of 100 patients with lung cancer and 50 healthy volunteers were collected ,and the levels of CD4 +CD25 +regulatory T cells and Th1and Th2 cytokines in peripheral blood were de-termined by flow cytometry.The correlation of CD4 +CD25 +regulatory T cells and Th1 and Th2 cytokines was analyzed .Results ①The proportion of Treg was significantly higher in advanced lung cancer patients (11.12 ±5.83)% than in healthy donors (7.46 ±3.07)%( P=0.003);②The proportion of Treg was lower in advanced lung cancer patients treated with chemotherapy (6.45 ±3.74)% compared to those patients without chemotherapy (11.12 ±5.83)% ( P<0.001);③ The level of Th1 and Th2 cytokines in advanced lung cancer patients and normal controls were :IFN-γ(8.56 ±3.62 vs 10.79 ±3.27,P=0.049)、IL-2(8.48 ±2.87vs10.22 ±4.03,P=0.03)、TNF-a(6.18 ±2.67vs8.14 ±2.87,P=0.007)、IFN-γ/IL-4(3.33 ±1.44vs4.09 ± 1.00,P=0.028)、IL-4(3.17 ±1.19vs2.45 ±0.43,P<0.001)、IL-6(3.88 ±2.08vs2.33 ±0.88,P<0.001)、IL-10(3.64 ± 1.73vs2.54 ±1.08,P=0.008).Th2 cytokines levels were significantly higher ,the difference was statistically significant (P<0.05).④No statistically significant relationships was found between Treg and IFN-γ,TNF-a,IL-2,IL-6(P>0.05).Treg levels were negatively correlated with Th1/Th2(P=0.003),but were positively correlated with IL-4 and IL-10(P<0.05).Conclusion The levels of CD4 +CD25 +regulatory T cells and Th2 cytokines were increased and Th 1 cytokines levels were decreased in pe-ripheral blood of advanced lung cancer patients .They may be together led to immune suppression and tumor progression in lung cancer patients .Monitoring the change of these indicators was very helpful for judging the curative effect and prognosis .It may be a new strategy to lung cancer to adjust the level of CD 4+CD25 +regulatory T cells and Th 1/Th2 cytokines .