摘要
目的:探究外周血1型辅助性T细胞(Th1)/Th2/Th17细胞相关细胞因子IL-2、IL-4、IL-6、IL-10、IFN-γ、TNF-α、IL-17A对Ⅲ~Ⅳ期肺鳞状细胞癌(LSCC)患者一线免疫治疗联合化疗疗效和预后的预测价值及其动态变化的意义。方法:回顾性分析2020年1月至2023年12月在内蒙古医科大学附属医院接受一线免疫治疗联合化疗的58例Ⅲ~Ⅳ期LSCC患者的临床资料,采集基线及治疗2、4、6周期后和疾病进展时的外周血,用流式细胞术检测Th1/Th2/Th17细胞分泌的细胞因子水平,用受试者工作特性曲线(ROC)确定各细胞因子基线的最佳截断值,据此将患者分为高、低表达组;根据RECIST 1.1标准,将患者分为客观缓解(ORR)[完全缓解(CR)+部分缓解(PR)]组、非ORR[疾病稳定(SD)+疾病进展(PD)]组、疾病控制(DCR)(CR+PR+SD)组和非DCR(即PD)组;根据PD-L1表达评分将患者分为PD-L1≥1%组和PD-L1<1%或未知组。比较组间疗效的差异;分析临床病理特征与疗效的相关性;用广义估计方程(GEE)评估细胞因子动态变化与疗效的关系;用Kaplan-Meier法绘制生存曲线,Log-Rank检验比较组间差异,COX比例风险回归模型进行单因素及多因素预后分析。结果:IL-2和IFN-γ高表达组患者的客观缓解率(ORR)显著高于低表达组患者(P<0.001)。IL-2、IFN-γ高表达组和IL-10、TNF-α低表达组患者的疾病控制率(DCR)均显著高于对应低/高表达组(P<0.001)。PD-L1≥1%组DCR显著高于PD-L1<1%或未知组(P<0.001)。动态分析显示,在4周期及6周期时,有效组患者血清中IL-6表达水平显著低于无效组(P<0.05),控制组IL-6表达水平显著低于未控制组(P<0.001);治疗前及6周期时有效组IFN-γ表达水平显著高于无效组(P<0.05),治疗前控制组IFN-γ表达水平显著高于未控制组(P<0.05)。生存分析显示,IL-2低表达组、IL-10高表达组、TNF-α高表达组和IFN-γ低表达组患者的中位PFS显著缩短(均P<0.05)。COX多因素分析证实,治疗前IL-2<2.45 pg/mL和IL-10≥3.52 pg/mL是PFS的独立危险因素。结论:外周血Th1/Th2/Th17细胞相关细胞因子的基线水平及动态变化对Ⅲ~Ⅳ期LSCC患者一线免疫治疗联合化疗的疗效和预后具有预测价值。
Objective:To investigate the dynamic changes and predictive value of peripheral blood T helper 1(Th1)/Th2/Th17-related cytokines IL-2,IL-4,IL-6,IL-10,IFN-γ,TNF-α,and IL-17A for treatment efficacy and prognosis in patients with stage Ⅲ-Ⅳ lung squamous cell carcinoma(LSCC)undergoing first-line immunotherapy combined with chemotherapy.Methods:Clinical data of 58 patients with stage Ⅲ-Ⅳ LSCC who received first-line immunotherapy combined with chemotherapy at the Affiliated Hospital of Inner Mongolia Medical University from January 2020 to December 2023 were retrospectively analyzed.Peripheral blood samples were collected at baseline,after 2,4,and 6 treatment cycles,and at disease progression.Th1/Th2/Th17 cytokine levels were measured using flow cytometry.Receiver operating characteristic(ROC)curves were used to determine optimal baseline cut-off values,based on which patients were divided into high-and low-expression groups.According to RECIST 1.1 criteria,patients were categorized into objective response rate(ORR;complete remission[CR]+partial remission[PR])and non-ORR(stable disease[SD]+progressive disease[PD])groups,as well as disease control rate(DCR;CR+PR+SD)and non-DCR(PD)groups.Based on PD-L1 expression scores,patients were divided into PD-L1≥1%and PD-L1<1%or unknown groups.Differences in treatment efficacy between groups were compared,and correlations between clinicopathological characteristics and efficacy were analyzed.Generalized estimating equations(GEE)were used to assess the relationship between cytokine dynamics and treatment efficacy.Survival curves were plotted using the Kaplan-Meier method,with Log-rank tests for intergroup comparisons.Univariate and multivariate prognostic analyses were performed using COX proportional hazards regression.Results:Patients with high baseline IL-2 or IFN-γexpression demonstrated significantly higher ORRs than those with low expression(P<0.001).The DCRs were significantly higher in the IL-2-high,IFN-γ-high,IL-10-low,and TNF-α-low groups compared with their counterparts(P<0.001).The DCRs were significantly higher in patients with PD-L1≥1%than those with PD-L1<1%or unknown group(P<0.001).Dynamic analysis revealed that serum IL-6 levels at cycles 4 and 6 were significantly lower in the response group and disease-controlled group compared with the non-response group and uncontrolled group(P<0.05 or P<0.001).IFN-γlevels were significantly higher in the response group than in the non-response group at baseline and cycle 6(P<0.05),and higher in disease-controlled group than in the uncontrolled group at baseline(P<0.05).Survival analysis showed significantly shorter median progression-free survival(PFS)in patients with low IL-2,high IL-10,high TNF-α,and low IFN-γexpression(all P<0.05).Multivariate COX analysis identified baseline IL-2<2.45 pg/mL and IL-10≥3.52 pg/mL as independent risk factors for PFS.Conclusion:Baseline levels and dynamic changes of peripheral blood Th1/Th2/Th17 cell-related cytokines have predictive value for treatment efficacy and prognosis in patients with stageⅢ–ⅣLSCC receiving first-line immunotherapy combined with chemotherapy.
作者
于欣静
李殊瑶
杨阳
乔晓娟
YU Xinjing;LI Shuyao;YANG Yang;QIAO Xiaojuan(Department of Oncology,the Affiliated Hospital of Inner Mongolia Medical University,Hohhot 010050,Inner Mongolia,China)
出处
《中国肿瘤生物治疗杂志》
2026年第3期313-322,共10页
Chinese Journal of Cancer Biotherapy
基金
内蒙古自治区自然科学基金(2021MS08153)
内蒙古自治区高校青年科技英才项目(NJYT22011)
内蒙古自治区高等学校科学研究项目(NJZY21596)
内蒙古自治区卫生健康科技计划项目(202201295)
内蒙古医科大学科技百万工程项目[YKD2020KJBW(LH)039]
内蒙古医科大学“致远”人才计划善学人才项目(ZY0202022)
内蒙古医学科学院公立医院科研联合基金科技项目(2024GLLH0311)。
