分析抗血管生成药物联合程序性死亡受体-1(programmed death-1, PD-1)单抗治疗非小细胞肺癌(nonsmall-cell lung cancer, NSCLC)的疗效及对T淋巴细胞亚群的影响。

选择2019年1月至2023年6月我院收治的64例NSCLC患者为对象，分为观察组33例和对照组31例。对照组行替雷利珠单抗或信迪利单抗静脉输液治疗，观察组在免疫治疗基础上采用贝伐珠单抗注射液静脉输液治疗或盐酸安罗替尼胶囊口服治疗。采用流式细胞术分析两组治疗前后外周血CD3^＋ T细胞、CD4^＋ T细胞、CD8^＋ T细胞、CD4^＋/CD8^＋ T细胞、CD4^＋/CD25^＋调节性T细胞百分比(%)。主要终点是根据实体肿瘤临床疗效评价标准1.1版评估的治疗反应和生存情况，计算疾病控制率和客观有效率；统计无进展生存期和总生存期。次要终点是根据国家癌症研究所不良事件通用术语标准4.0版的不良事件的发生情况和严重程度，以及生命体征和实验室的异常变化。

观察组客观有效14例(42.42%)高于对照组8例(25.81%)(P>0.05)；观察组疾病控制(90.91%)高于对照组(61.29%)(P<0.05)。两组治疗后CD4^＋、CD4^＋/CD8^＋细胞百分比较治疗前升高，观察组CD4^＋(40.48±9.86)%、CD4^＋/CD8＋(1.68±0.59)%高于对照组(34.03±7.48)%、(1.33±0.49)%，(P<0.05)；观察组治疗后CD8^＋(25.92±6.45)% 、CD4^＋CD25^＋(4.47±1.80)%较治疗前(33.62±9.55)%、(5.53±2.13)%降低，CD3^＋细胞百分比(71.66±9.90)%较治疗前(66.18±11.25)%升高(P<0.05)。64例患者不良免疫反应总发生36例(56.25%)，发生率超过10%的免疫不良反应有甲状腺功能障碍、血液/肺/胃肠道/肝毒性。≥G3不良反应的发生率观察组18.18%高于对照组12.90%(P>0.05)。Kaplan-Meier生存曲线分析显示，观察组中位无进展生存期为7.8个月长于对照组6.9个月(P<0.05)。

PD-1单抗联合抗血管生成药物治疗可改善机体的免疫抑制状态，有效提高晚期NSCLC患者疾病控制率并延长无进展生存期，治疗过程中不会增加免疫相关不良反应。

To analyze the effect of anti-angiogenic drugs combined with programmed death 1 (PD-1) blockade on the treatment of non-small cell lung cancer (NSCLC) and T lymphocyte subsets.

A total of 64 patients with advanced stage (confirmed by pathology or cytology as stage ⅢB/ⅢC/Ⅳ) NSCLC admitted to Xinjiang Production and Construction Corps Hospital (The Second Affiliated Hospital, School of Medicine, Shihezi University) from January 2019 to June 2023 were retrospectively selected as the subjects, including 33 patients in the observation group and 31 patients in the control group. Bevacizumab injection was administered intravenously or anrotinib hydrochloride capsules were administered orally. The proportion of peripheral plasma CD3⁺ T cells, CD4⁺ T cells, CD8⁺ T cells, CD4⁺ /CD8⁺ T cells, CD4⁺ /CD25⁺ regulatory T cells before and 6 weeks after treatment were analyzed by flow cytometry. The primary endpoint is to evaluate treatment response and survival based on the clinical efficacy evaluation criteria for solid tumors version 1.1, and calculate disease control rate and objective efficacy rate; Statistics on progression free survival and overall survival. The secondary endpoints are the occurrence and severity of adverse events, as well as abnormal changes in vital signs and laboratory parameters, according to the National Cancer Institute′s Common Terminology for Adverse Events 4.0. The follow-up deadline is December 2024.

There was no statistically significant difference in objective efficacy between the control group and the observation group (25.81% vs. 42.42%, P=0.162). However, the disease control rate of the control group patients was significantly lower than that of the observation group (61.29% vs. 90.91%, P=0.007). After treatment, the proportions of CD4⁺ and CD4⁺ /CD8⁺ in both groups increased compared to before treatment, and the observation group was higher than the control group (CD4⁺ : 40.48±9.86% vs. 34.03±7.48%, P=0.005; CD4⁺ /CD8⁺ : 1.68±0.59% vs. 1.33±0.49%, P=0.013). In addition, the proportions of CD8⁺ cells (25.92±6.45% vs. 33.62±9.55%) and CD4⁺ CD25⁺ (4.47±1.80% vs. 5.53±2.13%) in the observation group decreased compared to before treatment, while the percentage of CD3⁺ cells (71.66±9.90% vs. 66.18±11.25%) increased compared to before treatment (P<0.05). The incidence of adverse immune reactions was 56.25%, and more than 10% of adverse immune reactions include thyroid dysfunction, blood/lung/gastrointestinal/liver toxicity. Kaplan-Meier survival curve analysis showed that the median progression free survival in the observation group was 7.8 months, which was longer than the control group′s 6.9 months (Log Rank χ²=5.943, P=0.015).

The combination therapy of PD-1 monoclonal antibody and anti angiogenic drugs can improve the immune suppression status of the body, effectively improve the disease control rate and prolong the progression free survival of advanced NSCLC patients, and will not increase immune related adverse reactions during the treatment process.