血清细胞因子预测晚期NSCLC患者PD-1阻断剂治疗反应的临床研究

Clinical study of serum cytokines predicting response to PD-1 blockade in patients with advanced NSCLC

目的:探讨血清细胞因子与非小细胞肺癌(NSCLC)患者程序性死亡受体1(PD-1)阻断剂治疗反应和预后的相关性。方法:选取2015年1月至2019年10月91例晚期NSCLC患者(NSCLC组),TNMⅢ~Ⅳ期,均接受PD-1阻断剂治疗。另外选择同期在本院体检的90例健康志愿者作为对照组。采用AimPlex流式高通量多因子技术检测血清细胞因子水平。结果:与对照组相比,NSCLC组患者血清白细胞介素(IL)-4、IL-5、IL-8、γ干扰素(IFN-γ)、肿瘤坏死因子α(TNF-α)水平显著升高(P<0.05)。根据随访6个月的肿瘤反应,55例被评估为部分缓解或病情稳定的患者被归为有反应者。有反应者患者血清IL-5、IFN-γ水平显著高于无反应者(P<0.05),其预测治疗反应的受试者工作特征曲线下面积分别为0.708(95%CI 0.594~0.823)、0.825(95%CI 0.735~0.914)。经Logistic回归分析,血清IL-5、IFN-γ是PD-1阻断剂治疗反应的独立预测因子(P<0.05)。同样地,血清IL-5、IFN-γ与无病生存期、总生存期之间的相关性具有高度的统计学显著性和独立性(P<0.05)。结论:血清IL-5和IFN-γ水平可提供晚期NSCLC患者的预后信息,并可作为免疫治疗获益的预测指标。

Objective:To investigate the correlation between serum cytokines and the tumor response to programmed death receptor 1(PD-1)blockade,prognosis in patients with non-small cell lung cancer(NSCLC).Methods:A total of 91 patients with advanced NSCLC(TNM stageⅢtoⅣ)(NSCLC group)were recruited from January 2015 to October 2019,all of whom received PD-1 blockade.90 healthy volunteers in our hospital were selected as the control group.AimPlex flow cytometry was used to detect serum cytokine levels.Results:Compared with the control group,serum levels of interleukin(IL)-4,IL-5,IL-8,γ-interferon(IFN-γ)and tumor necrosis factorα(TNF-α)in NSCLC group were significantly increased(P<0.05).Fifty-five patients who were assessed as partial response or stable disease were classified as responders based on tumor response at 6 months of follow-up.The serum levels of IL-5 and IFN-γin responders were significantly higher than those in non-responders(P<0.05),and the area under the receiver operating characteristic curve for predicting treatment response was 0.708(95%CI 0.594-0.823)and 0.825(95%CI 0.735-0.914).Logistic regression analysis showed that serum IL-5 and IFN-γwere independent predictors of the response to PD-1 blockade(P<0.05).Similarly,the correlations between serum IL-5,IFN-γand disease-free survival,overall survival were highly significant and independent(P<0.05).Conclusion:Serum IL-5 and IFN-γlevels can provide prognostic information for patients with advanced NSCLC and can be used as predictors of immunotherapy benefit.