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-东南大学学报医学版

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

单位：临汾市中心医院呼吸与危重症医学科, 山西临汾 041000

分类号：R734.2;R453

出版年·卷·期（页码）：2022·41·第五期（668-675）

摘要：

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），TNM Ⅲ~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 stage Ⅲ to Ⅳ)(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 factor α(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-γ in 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-γ were independent predictors of the response to PD-1 blockade(P<0.05). Similarly, the correlations between serum IL-5, IFN-γ and disease-free survival, overall survival were highly significant and independent(P<0.05). Conclusion: Serum IL-5 and IFN-γ levels can provide prognostic information for patients with advanced NSCLC and can be used as predictors of immunotherapy benefit.

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