摘要
目的探讨晚期肺癌外周血淋巴细胞亚群表达与免疫治疗的关系,指导临床免疫治疗获益人群的筛选。方法回顾性分析2020—2022年间在南方医科大学深圳医院诊治的50例晚期肺癌患者的临床资料,选取同期30例健康体检人群作为对照组。采用流式细胞术分析外周血淋巴细胞亚群,对比肺癌治疗前淋巴细胞亚群数值与健康人群的差异,以及免疫检查点抑制剂(ICI)治疗前后(n=26)淋巴细胞亚群数值及比值变化,分析治疗有效患者在有效时及后续进展时淋巴细胞亚群变化情况,受试者工作特征(ROC)曲线预测曲线下面积(AUC)。结果与健康对照组相比,肺癌患者治疗前的淋巴细胞数、总T淋巴细胞数(CD3^(+))、辅助/诱导T淋巴细胞数(CD4^(+))、抑制/细胞毒T淋巴细胞数(CD8^(+))及B淋巴细胞数和自然杀伤细胞(NK细胞)数明显降低(均P<0.05)。26例患者进行了ICI±其他抗肿瘤药物治疗,与治疗前相比,治疗后患者的外周血CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)比值明显升高,B淋巴细胞数明显下降(均P<0.05)。对于治疗后有免疫应答的患者,应答时外周血淋巴细胞亚群中的CD3^(+)、CD4^(+)及CD4^(+)/CD8^(+)比值较进展时明显升高,而NK细胞水平明显下降(均P<0.05)。ROC曲线分析表明CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)、NK细胞对晚期肺癌患者6个月无进展生存率预测的AUC分别为0.656、0.725、0.731、0.653,截点值分别为67.33%、38.14%、18.33、1.77%。结论检测晚期肺癌外周血淋巴细胞亚群对患者免疫功能状态具有良好的预测效果,同时有助于评估ICI疗效。
Objective To investigate the lymphocyte subset in peripheral blood and its association with immunotherapy in advanced lung cancer,so as to guide the screening of patients who benefit from clinical immunotherapy.Methods A total of 50 patients with advanced lung cancer treated in Shenzhen Hospital of Southern Medical University from August 2020 to January 2022 were retrospectively analyzed,and 30 healthy people were selected as control.Flow cytometry(FCM)was used to test peripheral blood lymphocyte subsets,the difference between therapy-naïve lung cancer patients and healthy group was compared.Among them,26 patients treated with immune checkpoint inhibitors(ICIs)had the lymphocyte subsets results both before and after treatment.The changes of lymphocyte subsets ratio were compared,and the changes of lymphocyte subsets during effective and progressive period were also analyzed.Area under the curve(AUC)was predicted by receiver operating characteristic(ROC)curve.Results Compared to the healthy controls,the absolute number of lymphocytes,CD3^(+)T cells,CD4^(+)T cells,NK cells and B cells in peripheral blood of lung cancer patients before treatment were significantly decreased(P<0.05).Twenty-six patients were treated with ICIs with or without other anti-tumor drugs,and compared with treatment-naive,the ratios of CD3^(+),CD4^(+),CD4^(+)/CD8^(+)in peripheral blood were increased after immunotherapy,and the ratio of B cells was significantly decreased(P<0.05).For patients with immune response after treatment,the ratios of CD3^(+),CD4^(+)and CD4^(+)/CD8^(+)were decreased compared with the progressive stage,while the ratio of NK was significantly increased(P<0.05).The result of ROC analysis showed that the AUCs of CD3^(+),CD4^(+),CD4^(+)/CD8^(+)and NK were 0.656,0.725,0.731 and 0.653,and the cut-off values were 67.33%,38.14%,18.33,1.77%,respectively.Conclusions The detection of lymphocyte subsets is a good reflection on the immune function of patients with advanced lung cancer,and its prediction of efficacy with ICIs is worthy of further analysis.
作者
洪翔婵
吴小亮
Hong Xiangchan;Wu Xiaoliang(Department of Oncology,Shenzhen Hospital of Southern Medical University,Shenzhen 518100,China)
出处
《中华转移性肿瘤杂志》
2022年第4期298-305,共8页
Chinese Journal of Metastatic Cancer
基金
国家自然科学基金青年项目(81902348)
关键词
晚期肺癌
免疫检查点抑制剂
淋巴细胞亚群
免疫治疗
Advanced lung cancer
Immune checkpoint inhibitors
Lymphocyte subsets
Immunotherapy
