晚期肺腺癌患者接受一线程序性死亡受体1抗体联合化疗疗效的性别差异OACSTPCD
Sex differences in the efficacy of first-line PD-1 blockade plus chemotherapy in patients with advanced lung adenocarcinoma
目的 探讨晚期肺腺癌患者接受一线程序性死亡受体 1(programmed death-1,PD-1)抗体联合化疗疗效的性别差异,并初步分析性别影响疗效的潜在生物学机制.方法 回顾性分析 2018 年 10 月至 2023 年 10 月在同济大学附属上海市肺科医院就诊的 163 例无驱动基因变异晚期肺腺癌患者的临床病理特征和生存随访资料,其中 103 例患者接受一线PD-1 抗体联合化疗(男性 51 例,女性 52 例),60 例患者接受一线标准含铂双药化疗(男性 39 例,女性 21 例).根据性别分组,比较不同性别患者的临床特征、疗效、无进展生存期(progression-free survival,PFS)和总生存期(overall survival,OS).采用Kaplan-Meier法绘制男性组和女性组患者的生存曲线,log-rank检验进行显著性评价;采用Cox比例风险模型分析PFS和OS的影响因素;采用多色免疫荧光染色法分析不同性别患者基线肿瘤样本程序性死亡受体配体 1(programmed death-ligand 1,PD-L1)、CD8、CD68、CD4、FOXP3 蛋白表达水平的差异.结果 接受一线PD-1 抗体联合化疗的患者中,女性组和男性组的中位PFS分别为 13.0 个月和 6.8 个月(HR=0.39,95%CI 0.25～0.62;P＜0.01);中位OS分别为 46.2 个月和 17.3 个月(HR=0.30,95%CI 0.18～0.50;P＜0.01).接受一线化疗的患者中,女性组和男性组的中位PFS分别为 5.7 个月和 5.5 个月,中位OS分别为 21.7 个月和 17.7 个月,差异均无统计学意义.Cox比例风险模型结果显示,性别是患者接受一线PD-1 抗体联合化疗后PFS和OS的独立影响因素(P＜0.05).多色免疫荧光染色分析结果显示,女性肺腺癌患者基线肿瘤样本CD8 表达水平显著高于男性患者(P＜0.05),而PD-L1、CD68、CD4、FOXP3 表达水平差异无统计学意义.结论 相较于男性患者,女性肺腺癌患者从一线PD-1 抗体联合化疗中获益更多;女性患者基线肿瘤样本CD8表达水平显著高于男性患者,可能是获益更多的潜在机制.
Objective To explore the impact of sex on the efficacy of first-line programmed death-1(PD-1)blockade plus chemotherapy in patients with advanced lung adenocarcinoma and its potential biological mechanisms.Methods The clinical and pathological characteristics and follow-up data of 163 patients with advanced lung adenocarcinoma without driver gene alterations at Shanghai Pulmonary Hospital affiliated to Tongji University from October 2018 to October 2023 were retrospectively collected.Among them,103 patients received first-line PD-1 blockade plus chemotherapy(51 males and 52 females)and 60 patients received first-line standard platinum-based doublet chemotherapy(39 males and 21 females).Patients were divided into male group and female group.Clinical characteristics,efficacy,progression-free survival(PFS),and overall survival(OS)were compared between the two groups.Kaplan-Meier method was used to plot the survival curves of male and female patients,and log-rank test was used for significance evaluation.Cox proportional hazards model was used to analyze the factors influencing PFS and OS.Multiplex immunofluorescence(mIF)assays were used to analyze the differences of protein expression levels of programmed death-ligand 1(PD-L1),CD8,CD68,CD4,and FOXP3 between male and female groups in baseline tumor sample.Results In patients receiving first-line PD-1 blockade plus chemotherapy,the median PFS in female group and male group was 13.0 months and 6.8 months,respectively(HR=0.39,95% CI 0.25-0.62;P＜0.01).The median OS in female group and male group was 46.2 months and 17.3 months,respectively(HR=0.30,95% CI 0.18-0.50;P＜0.01).In patients receiving first-line chemotherapy,the median PFS in female group and male group was 5.7 months and 5.5 months,respectively(P＞0.05);the median OS in female group and male group was 21.7 months and 17.7 months,respectively(P＞0.05).The results of the Cox proportional hazards model showed that sex was an independent factor influencing PFS and OS in patients receiving first-line PD-1 blockade plus chemotherapy(P＜0.05).The results of mIF showed that pretreatment tumor samples of female patients had a significantly higher expression level of CD8 than male patients(P＜0.05),while the expression level of PD-L1,CD68,CD4 and FOXP3 was similar between female and male groups.Conclusions Compared to male patients,female patients with advanced lung adenocarcinoma benefit more from the first-line PD-1 blockade plus chemotherapy.The increased expression level of CD8 in pretreatment tumor samples of female patients would be the potential mechanism.
申辉;张洪涛;王浩伟;蒋涛;赵凤德
阜阳市第二人民医院呼吸与危重症医学科,阜阳 236015阜阳市第二人民医院肿瘤内科,阜阳 236015同济大学附属上海市肺科医院肿瘤科,上海 200433
临床医学
肺腺癌程序性死亡受体1抗体化疗性别
lung adenocarcinomaprogrammed death-1 blockadechemotherapysex
《中国临床医学》 2024 (005)
757-764 / 8
上海市 2023 年度"科技创新行动计划"医学创新专项项目(23Y11904100).Supported by Shanghai 2023"Science and Technology Innovation Action Plan"Medical Innovation Special Project(23Y11904100).
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