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

doi:10.3969/j.issn.1006-6233.2024.09.013

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摘要 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。

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关键词 ：肺癌, T淋巴细胞, 中性粒细胞与淋巴细胞比值, 程序性死亡受体-1

Abstract：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.

Key words： Lung cancer T lymphocytes Neutrophil-to-lymphocyte ratio Programmed death receptor-1

基金资助:2022年度安徽省卫生健康科研项目,(编号:AHWJ20226099)

引用本文:

吕志芳, 王明, 程飞飞, 王玲, 钱建伟. 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[J]. 河北医学, 2024, 30(9): 1483-1487.
LV Zhifang, WANG Ming, CHENG Feifei, et al. Study on the Relationship between Neutrophils/Lymphocytes CD4⁺/CD8⁺ and the Efficacy and OS of PD-1 Inhibitor Immunotherapy for Lung Cancer. HeBei Med, 2024, 30(9): 1483-1487.

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http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2024.09.013 或 http://www.hbyxzzs.cn/CN/Y2024/V30/I9/1483

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