[摘 要] 目的：探索淋巴细胞亚群对非小细胞肺癌（NSCLC）患者接受程序性死亡受体1（PD-1）单抗联合化疗的疗效预测及 预后评估的价值。方法：回顾性分析2022年1月至2023年12月在兰州大学第二医院确诊的接受PD-1单抗联合化疗的50例 NSCLC患者的临床资料，收集患者治疗前及治疗2周期后的外周血淋巴细胞亚群（包括总T细胞、CD4+ T细胞、CD8+ T细胞、NK 细胞、总B淋巴细胞、CD4+ /CD8+ T细胞比值等）的数据。治疗2周期后进行影像学检查评价治疗的疗效，分为疾病控制（DC）组和 疾病进展（PD）组。使用卡方检验、秩和检验和Logistic回归分析淋巴细胞亚群表达水平与NSCLC患者近期疗效的关系，采用 Kaplan-Meier法分析无进展生存期（PFS）预测疗效的价值。结果：PD-1单抗联合化疗对NSCLC患者的免疫状态产生了显著影 响，接受免疫联合化疗后，患者外周血CD4+ T细胞、CD4+ /CD8+ T细胞比值均显著升高（均P < 0.01），CD8+ T细胞下降。近期疗效 显示，DC组患者血清CD4+ T细胞比例及CD4+ /CD8+ T细胞比值均高于PD组（均P < 0.01）。Logistic多因素分析显示，CD4+ /CD8+ T 细胞比值是PD-1单抗联合化疗疗效的独立影响因素。通过ROC曲线分析，CD4+ /CD8+ T细胞比值变化量AUC为0.820 > 0.5，截断 值为0.15，CD4+ /CD8+ T细胞比值变化量 ≥ 0.15的患者的PFS更长。结论：晚期NSCLC患者外周血中CD4+ T细胞和CD8+ T细胞 比例、CD4+ /CD8+ T细胞比值可以预测PD-1单抗联合化疗的疗效和预后。

[Abstract] Objective: To explore the value of lymphocyte subsets in predicting the efficacy and prognosis of non-small cell lung cancer (NSCLC) patients receiving programmed death receptor 1 (PD-1) monoclonal antibody (mAb) combined with chemotherapy. Methods: A retrospective analysis was conducted on the clinical data of 50 NSCLC patients diagnosed and treated with PD-1 mAb combined with chemotherapy at the Second Hospital of Lanzhou University from January 2022 to December 2023. Peripheral blood lymphocyte subsets (including total T cells, CD4+ T cells, CD8+ T cells, NK cells, total B lymphocytes, and CD4+ /CD8+ T cell ratio) were collected before and after two cycles of treatment. After two cycles of treatment, imaging examination was performed to evaluate the therapeutic efficacy, dividing patients into disease control (DC) group and disease progression (PD) group. The relationship between lymphocyte subset levels and the short-term efficacy in NSCLC patients was analyzed using chi-square test, rank sum test, and Logistic regression analysis. The value of lymphocyte subsets in predicting patients’ progression-free survival (PFS) was explored using KaplanMeier method. Results: PD-1 mAb combined with chemotherapy significantly influenced the immune status of NSCLC patients. After treatment, the peripheral blood CD4+ T cells and CD4+ /CD8+ T cell ratio significantly increased (both P < 0.01), while the level of CD8+ T cells decreased. In terms of short-term efficacy, the proportion of CD4+ T cells and the CD4+ /CD8+ T cell ratio in the DC group were significantly higher than those in the PD group (both P < 0.01). Logistic multivariate analysis showed that the CD4+ /CD8+ T cell ratio was an independent factor affecting the efficacy of PD-1 mAb combined with chemotherapy. ROC curve analysis showed that the area under the curve (AUC) for CD4?/CD8? T cell ratio variation was 0.820 (> 0.5), with a cut-off value of 0.15. Patients with a the CD4+/CD8+ T cell ratio increase of ≥ 0.15 had a longer PFS. Conclusion: The proportion of CD4+ T cells, CD8+ T cells, and the CD4+/CD8+ T cell ratio in peripheral blood can predict the efficacy and prognosis of PD-1 mAb combined with chemotherapy in advanced NSCLC patients.

北京医学奖励基金会基金（No. YXJL-2022-0105-0112）