记忆T细胞在行放射治疗的非小细胞肺癌患者中的表达及其预后预测价值

Expression and prognostic value of memory T lymphocyte in patients with non-small cell lung cancer following radiotherapy

目的:分析记忆T细胞在行放射治疗的非小细胞肺癌(NSCLC)患者中的表达及其对预后的预测价值。方法:收集2010年2月至2012年5月浙江省宁波市医疗中心李惠利医院共46例接受放射治疗的NSCLC患者和50名健康体检者。应用流式细胞术检测外周血CD4^+、CD8^+的中央型记忆T细胞(T_(CM))和效应型记忆T细胞(T_(EM))的表达。采用多因素Cox回归模型分析患者临床特征及记忆T细胞变化与总生存时间的相关性,并采用Kaplan-Meier法绘制生存曲线。结果:NSCLC患者放射治疗前外周血CD4^+T_(CM)、CD4^+T_(EM)、CD8^+T_(CM)和CD4^+/CD8^+T_(EM)比值较健康对照组低,CD4^+/CD8^+T_(CM)比值较健康对照组高(均P<0.05);放射治疗4周时,NSCLC患者外周血CD4^+T_(CM)、CD4^+T_(EM)、CD8^+T_(CM)和CD4^+/CD8^+T_(EM)比值较放射治疗前明显降低(均P<0.05),而CD8^+T_(EM)和CD4^+/CD8^+T_(CM)比值较放射治疗前升高(均P<0.05);放射治疗12周时,NSCLC患者外周血CD4^+T_(CM)、CD4^+T_(EM)和CD8^+T_(CM)较放射治疗4周时升高(均P<0.05)。多因素Cox回归分析结果显示,放射治疗后CD4^+T_(CM)的变化趋势与NSCLC患者的总生存时间有相关性(95%CI:1.135~2.994,P<0.01)。放射治疗后CD4^+T_(CM)呈下降趋势者的存活率为23.1%,总生存时间为10.7个月(95%CI:0.29~12.41);CD4^+T_(CM)保持稳定者的存活率为52.7%,总生存时间为27.4个月(95%CI:0.00~31.26);CD4^+T_(CM)上升者的存活率为66.4%,总生存时间为37.4个月(95%CI:0.33~29.21)。结论:NSCLC患者放射治疗后初期表现出明显的免疫抑制,之后有逐渐改善的趋势。放射治疗后记忆T细胞的变化趋势对患者的预后有一定的预测价值。

Objective : To investigate the expression and prognostic value of memory T lymphocyte in patients with non-small cell lung cancer( NSCLC) following radiotherapy. Methods : Forty-six patients with NSCLC receiving radiotherapy in Ningbo Medical Center Lihuili Hospital from February 2010 to May 2012 were enrolled in the study and 50 healthy subjects served as the control group. The central memory T cell( Tcm) and effector memory T cell(T_(EM)) in peripheral blood CD4^+, CD8^+ cells were detected by flow cytometry. Survival of patients was analyzed by Kaplan-Meier curve, and the relationship between clinical features, memory T lymphocyte changes and overall survival was analyzed by multivariate Cox regression model. Results: CD4^+T_(CM), CD4^+ T_(EM), CD8^+ T_(CM) levels and CD4^+/CD8^+ T_(EM) of NSCLC patients were significantly lower than those of the control group, while CD4^+/CD8^+ T_(CM) was significantly higher than that of the control group( all P < 0. 05). In NSCLC patients,CD4^+ T_(CM), CD4^+ T_(EM) and CD8^+ T_(CM)were decreased and CD8^+ T_(EM) levels were increased4 weeks after radiotherapy(all P < 0.05); CD4^+ T_(CM), CD4^+ T_(EM) and CD8^+ T_(CM) at12-week after radiotherapy were increased significantly compared with those at 4-week after radiotherapy( all P < 0.05). Multivariate Cox regression analysis showed that the change of CD4^+ T_(CM) after radiotherapy was correlated with the overall survival(95%CI: 1. 135-2.994, P<0.01). The survival rate and overall survival time for patients with decreasing CD4^+ T_(CM) were 23. 1% and 10. 7 months(95% CI: 0. 29-12. 41),while those of patients with stable CD4^+ T_(CM) were 52.7% and 27.4 months(95% CI:0.00-31.26), and those of patients with increasing CD4^+T_(CM) were 66.4% and 37.4 months(95% CI: 0.33-29.21), respectively. Conclusions: NSCLC patients show a significant immunosuppression at the initial stage after radiotherapy, and then a gradual improvement. Change of memory T lymphocyte after radiotherapy can be used to help predicting the prognosis of the patients.