晚期非小细胞肺癌患者DC-CIK治疗前的免疫状态与预后的关系

Relationship between prognosis and immune status of patients with advanced NSCLC before DC-CIK immunotherapy

目的探讨晚期非小细胞肺癌(NSCLC)患者树突状细胞-细胞因子诱导的杀伤细胞(dendritic cellcytokine induced killers,DC-CIK)治疗前外周血CD4+CD25+CD127-调节性T细胞(regulatory T cells,TRegs)、CD3+CD56+细胞因子诱导的杀伤细胞(cytokine induced killer cells,CIKs)、CD4+/CD8+T细胞比值与预后的关系。方法采用流式细胞仪技术检测45例晚期NSCLC患者DC-CIK治疗前、后外周血CD4+CD25+CD127-TRegs、CD3+CD56+CIKs、CD4+和CD8+T细胞,并与患者临床特征进行相关分析;采用Cox回归模型分析治疗前CD4+CD25+CD127-TRegs、CD3+CD56+CIKs、CD4+/CD8+T细胞比值对患者预后的影响。结果晚期NSCLC患者DC-CIK治疗前、后比较,治疗后患者外周血CD4+T细胞减少,CD8+T细胞增多,CD4+/CD8+T细胞比值下降,差异均有统计学意义(均P<0.05);原发病灶瘤体最长直径越大,患者治疗前外周血TRegs越多,CIKs越少(均P<0.05);生存分析显示,治疗前TRegs越多,患者预后越差,生存期越短,且TRegs>7×109/L影响患者的生存(P<0.05)。结论晚期NSCLC患者外周血TRegs是判断预后的独立预测指标。

Objective To investigate the relationship between the immune status before dendritic cell-cytokine induced killer （DC-CIK） biotherapy and the prognosis of patients with advanced non-small-cell lung cancer （NSCLC）. Methods Forty-five patients with advanced NSCLC received DC-CIK therapy. The levels of CD4^＋ CD25^＋CD127^- regulatory T cells （ TRegs ） and CD3^＋CD56^＋ CIKs and the ratio of CD4^＋/CD8^＋ T cells in peripheral blood were measured with flow cytometry. Clinicopathological characteristics of patients were evaluated by Spearman analysis. Prognostic factors for advanced NSCLC were evaluated by Cox regression. Results The ratio of CD4^ ＋/CD8^＋ T cells in peripheral blood after CD-CIK therapy declined significantly （P 〈 0.05 ）. CD4^ ＋ CD25^＋ CD127 ^- TRegs level was positively and CD3^＋ CD56 ^＋ CIKs level was negatively correlated with tumor size （ both P 〈 0. 05 ）. The level of CD4^＋CD25^＋ CD127 ^- TRigs before therapy was negatively correlated with survival rate （P 〈 0.05 ）. Conclusion The level of regulatory T cells in peripheral blood is an independent prognostic factor for patients with advanced NSCLC.