中性粒细胞/淋巴细胞CD4^(+)/CD8^(+)与PD-1抑制剂免疫治疗肺癌疗效及OS的关系研究

Study on the Relationship between Neutrophils/Lymphocytes CD4^(+)/CD8^(+)and the Efficacy and OS of PD-1 Inhibitor Immunotherapy for Lung Cancer

目的:观察肺癌患者采用程序性死亡受体-1(PD-1)抑制剂治疗后不同疗效患者中性粒细胞/淋巴细胞(NLR)、CD4^(+)/CD8^(+)水平变化情况,并分析其水平变化与疗效及总生存时间(OS)的相关性。方法:纳入94例本院2019年12月至2022年3月收治的肺癌患者,观察实施PD-1治疗后不同疗效患者机体NLR、CD4^(+)/CD8^(+)水平变化情况,分析其与免疫治疗后不同疗效及随访2年后OS的关联性。结果:经PD-1抑制剂治疗后不同疗效患者NLR、CD4^(+)/CD8^(+)水平比较差异有统计学意义(P<0.05),其中CR、PR组与SD、CD组NLR、CD4^(+)/CD8^(+)水平比较差异有统计学意义(P<0.05),SD组与PD组NLR水平比较差异有统计学意义(P<0.05);单因素分析显示患者免疫治疗后有效组与无效组患者在病理类型、TNM分期、分化程度、年龄及NLR、CD4^(+)/CD8^(+)水平上比较差异有统计学意义(P<0.05);Logistic回归模型发现:小细胞型、TNM分期(Ⅳ期)、分化程度(低分化)和年龄较高、高水平NLR是免疫治疗疗效不佳的危险因素(P<0.05),CD4^(+)/CD8^(+)高水平则是免疫治疗疗效不佳的保护因素(P<0.05);ROC曲线显示:NLR、CD4^(+)/CD8^(+)评估疗效的曲线下面积(AUC)分别为0.785、0.777,而NLR联合CD4^(+)/CD8^(+)评估疗效的AUC为0.871,明显高于单项指标,差异有统计学意义(P<0.05);Spearman相关性分析显示:NLR与OS呈负相关,差异有统计学意义(r=-0.341,P<0.05),而CD4^(+)/CD8^(+)与OS呈正相关,差异有统计学意义(r=0.323,P<0.05)。结论:肺癌经PD-1抑制剂治疗有效患者机体NLR水平较低,CD4^(+)/CD8^(+)水平较高,且对免疫治疗疗效具有一定的评估价值,同时也与OS有一定的关联性。

Objective:To observe the changes in neutrophil/lymphocyte ratio(NLR)and CD4^(+)/CD8^(+)in patients with lung cancer after treatment with programmed death receptor-1(PD-1)inhibitor,and to analyze the correlation between changes of two indicators and efficacy and overall survival time(OS).Methods:A total of 94 patients with pulmonary cancer were included in the hospital from December 2019 to March 2022.The changes of NLR and CD4^(+)/CD8^(+)were observed among patients with different efficacies after PD-1 treatment,and the association with different efficacies after immunotherapy and OS after 2 years of follow-up was analyzed.Results:There were statistically significant differences in NLR and CD4^(+)/CD8^(+)among patients with different efficacies after PD-1 inhibitor treatment(P<0.05).The NLR and CD4^(+)/CD8^(+)in the CR group and PR group were statistically different from those in the SD group and CD group(P<0.05),and there was a statistical significance in NLR between the SD group and PD group(P<0.05).Univariate analysis showed that the pathological type,TNM staging,differentiation degree,age,NLR and CD4^(+)/CD8^(+)were statistically significant between the effective group and the ineffective group after immunotherapy(P<0.05).Logistic regression model found that small cell type,TNM staging(stage IV),differentiation degree(low differentiation),older age,and high NLR were risk factors for poor efficacy of immunotherapy(P<0.05),while high CD4^(+)/CD8^(+)was a protective factor for poor efficacy of immunotherapy(P<0.05).ROC curve showed that the areas under the curves(AUCs)of NLR and CD4^(+)/CD8^(+)in evaluating the efficacy were 0.785 and 0.777 respectively,and the AUC of NLR combined with CD4^(+)/CD8^(+)was 0.871,which was significantly higher than that of single index(P<0.05).Spearman correlation analysis suggested that NLR was negatively correlated with OS(r=-0.341,P<0.05),and CD4^(+)/CD8^(+)was positively correlated with OS(r=0.323,P<0.05).Conclusion:The NLR is lower while the CD4^(+)/CD8^(+)is higher among patients with pulmonary cancer who are with effective PD-1 inhibitor treatment,and the two indexes have certain evaluated values on the efficacy of immunotherapy and also have a certain association with OS.