基于PD-1/PD-L1探究替雷利珠单抗对紫杉醇联合铂类一线治疗中晚期肺鳞癌的协同增效作用

The synergistic effect of tirellizumab in the first-line treatment of advanced lung squamous cell carcinoma with paclitaxel and platinum based on PD-1/PD-L1 expression

摘要:

目的 基于PD-1/PD-L1探究替雷利珠单抗对紫杉醇联合铂类一线治疗中晚期肺鳞癌的协同增效作用，为临床治疗提供参考依据。方法 收集2020年3月至2023年3月我院收治的120例中晚期肺鳞癌患者的临床资料进行回顾性分析，将符合纳入、排除标准并应用替雷利珠单抗与紫杉醇联合铂类一线治疗的60例患者设为观察组，按1∶1的比例选择60例紫杉醇联合铂类一线治疗的患者设为对照组。比较两组患者的疗效、毒副反应、肿瘤标志物［鳞状细胞癌抗原（SCCA）、细胞角蛋白19可溶性片段（CYFRA21-1）及癌胚抗原（CEA）］、T淋巴细胞亚群（CD4+、CD8+及CD4+/CD8+）、PD-1/PD-L1信号通路相关蛋白（PD-1、PD-L1），统计并比较两组远期生存率。结果 观察组患者ORR及DCR均显著高于对照组（P<0.05）；观察组患者胃肠道反应、脱发及白细胞减少的发生率均显著低于对照组（P<0.05）。治疗2个疗程后及治疗4个疗程后，观察组患者血清CEA、CYFRA21-1、SCCA水平均显著低于对照组（P<0.05）；观察组患者CD4+水平和CD4+/CD8+均显著高于对照组，而CD8+水平显著低于对照组（P<0.05）；观察组患者外周血CD4+ T细胞PD-1、PD-L1表达水平均显著低于对照组（P<0.05）。观察组患者2年生存率显著高于对照组，总生存期（OS）及无进展生存期（PFS）显著长于对照组（P<0.05）。结论 替雷利珠单抗协同紫杉醇和铂类一线治疗中晚期肺鳞癌可提高疗效，改善患者机体免疫功能，减轻毒副反应，延长患者生存期，其机制可能与调节PD-1/PD-L1通路相关。

Abstract:

Objective To explore the synergistic effect of tislelizumab in the first-line treatment with paclitaxel and platinum for the advanced lung squamous cell carcinoma patients based on PD-1/PD-L1 expression, and to provide reference for clinical treatment.Methods Clinical data of 120 patients with advanced lung squamous cell carcinoma in our hospital from March 2020 to March 2023 were collected for retrospective analysis. 60 patients who met the inclusion and exclusion criteria receiving first-line treatment with tislelizumab and paclitaxel combined with platinum were set as the observation group, and 60 patients receiving first-line treatment with paclitaxel combined with platinum were chosen as the control group. The efficacy, toxicity, and the long-term survival rate were compared between the two groups, as well as the levels of tumor markers [squamous cell carcinoma antigen (SCCA), soluble fragment of cytokeratin 19 (CYFRA21-1) and carcinoembryonic antigen (CEA)], T lymphocyte subsets (CD4+, CD8+, and CD4+/CD8+), PD-1/PD-L1 signaling pathway-related indicators (PD-1, PD-L1).Results The objective remission rate (58.33%) and disease control rate (78.33%) in observation group were higher than those in control group (respectively 36.67% and 56.67%) (P<0.05). The incidence of gastrointestinal reaction (20.00%), alopecia (15.00%) and leukopenia (18.33%) in observation group was lower than that in control group (36.67%, 31.67%, 35.00%, respectively) (P<0.05). After 2 and 4 courses of treatment, the levels of CEA, CYFRA21-1 and SCCA in observation group were all lower than those in control group (P<0.05). The proportion of CD4+ and the CD4+/CD8+ in observation group were higher than those in control group, while the proportion of CD8+ was lower than that in control group (P<0.05). Moreover, the levels of PD-1 and PD-L1 in CD4+ T cells in the peripheral blood were lower in observation group than in control group (P<0.05). The 2-year survival rate of the observation group was significantly higher than that of the control group, and the overall survival (OS) and progression-free survival (PFS) were significantly longer than those of the control group (P<0.05).Conclusion Tislelizumab can play a synergistic role in combination with paclitaxel and platinum in the first-line treatment of middle and advanced lung squamous cell carcinoma, improve immunity, reduce toxic and side effects, and prolong the long-term survival rate of patiens. It may be related to the regulation of PD-1/PD-L1 pathway.