外周血淋巴细胞亚型预测晚期肺癌患者免疫相关不良反应的价值  

Value of peripheral blood lymphocyte subset to the prediction of immune-related adverse events in patients with advanced lung cancer

作　　者：李鹏 秦鹏 付晓敏 王启鸣 LI Peng;QIN Peng;FUXiao-min;WANG Qi-ming(Department of Medical Oncology,the Affiliated Cancer Hospital of Zhengzhou University,Henan Cancer Hospital,Zhengzhou,Henan 450008,China;Department of Immunotherapy,the Affiliated Cancer Hospital of Zhengzhou University,Henan Cancer Hospital,Zhengzhou,Henan 450008,China)

机构地区：[1]郑州大学附属肿瘤医院河南省肿瘤医院肿瘤内科,河南郑州450008 [2]郑州大学附属肿瘤医院河南省肿瘤医院免疫治疗科,河南郑州450008

出　　处：《中华实用诊断与治疗杂志》2023年第4期367-371,共5页Journal of Chinese Practical Diagnosis and Therapy

基　　金：河南省中青年卫生健康科技创新领军人才培养项目(YXKC2020009)。

摘　　要：目的观察晚期肺癌患者免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)治疗前、后外周血淋巴细胞亚型变化,探讨其与免疫相关不良反应(immune-related adverse events,irAEs)的关系。方法34例晚期肺癌患者均接受ICIs治疗,包括程序性死亡受体1(programmed death-1,PD-1)抑制剂单药,化疗联合PD-1抑制剂或小分子抗血管生成药物联合PD-1抑制剂治疗。ICIs治疗前、第3个周期治疗前应用流式细胞仪检测外周血淋巴细胞亚型,包括Treg细胞、B细胞、NK细胞、CD45^(+)T细胞、CD8^(+)T细胞、CD4^(+)T细胞、CD3^(+)T细胞绝对值及PD-1^(+)/CD45^(+)T细胞、PD-1^(+)/CD8^(+)T细胞、PD-1^(+)/CD4^(+)T细胞、PD-1^(+)/CD3^(+)T细胞百分比和CD4^(+)/CD8^(+)比值12项指标,并计算各项指标治疗前后差值。34例患者根据治疗2个周期后是否发生irAEs分为不良反应组10例和无不良反应组24例。分别采用单因素和多因素logistic回归构建治疗前12项外周血淋巴细胞亚型(模型1)、治疗前Treg细胞绝对值(模型2)预测晚期肺癌患者发生irAEs的预测模型,采用R 4.2.0软件绘制ROC曲线,评估模型1、模型2预测晚期肺癌患者发生irAEs的效能。结果34例患者中10例发生irAEs(29.4%)。治疗前不良反应组Treg细胞绝对值[6.60(5.45,7.63)个/μL]低于无不良反应组[7.85(6.88,9.85)个/μL](U=61.500,P=0.025),其他11项指标与无不良反应组比较差异均无统计学意义(P>0.05);治疗后不良反应组12项指标与无不良反应组比较差异均无统计学意义(P>0.05)。不良反应组、无不良反应组治疗后Treg细胞绝对值均高于治疗前(P<0.05),PD-1^(+)/CD45^(+)T细胞百分比、PD-1^(+)/CD8^(+)T细胞百分比、PD-1^(+)/CD4^(+)T细胞百分比、PD-1^(+)/CD3^(+)T细胞百分比均低于治疗前(P<0.05),2组治疗后其他7项指标与同组治疗前比较差异均无统计学意义(P>0.05)。不良反应组治疗前后12项指标差值与无不良反应组比较差异均无统计学意义(P>0.05)�Objective To observe the changes of peripheral blood lymphocyte subtypes after treatment with immune checkpoint inhibitors(ICIs)in patients with advanced lung cancer,and to explore its relationship with immune-related adverse events(irAEs).Methods Thirty-four patients with advanced lung cancer were treated with ICIs,including PD-1inhibitor monotherapy,chemotherapy in combination with PD-1inhibitors,or small molecule antiangiogenic drugs in combination with PD-1inhibitors.Flow cytometry was used to detect the peripheral lymphocyte subsets as the absolute values of Treg cells,B cells,NK cells,CD45^(+)T cells,CD8^(+)T cells,CD4^(+)T cells and CD3^(+)T cells,the percentages of PD-1^(+)/CD45^(+)T cells,PD-1^(+)/CD8^(+)T cells,PD-1^(+)/CD4^(+)T cells and PD-1^(+)/CD3^(+)T cells,and the ratio of CD4^(+)/CD8^(+)before and after the third cycle of ICIs treatment.The difference values before and after treatment were calculated.Based on whether irAEs occurred after 2cycles of treatment,34patients were divided into irAEs group(n=10)and non-irAEs group(n=24).Univariate and multivariate logistic regression analyses were used to construct a model of the above 12peripheral lymphocyte subtypes before treatment(model 1)and a model of the absolute value of Treg cells before treatment(model 2)to predict irAEs in patients with advanced lung cancer.The ROC curves were plotted with R4.2.0software to evaluate the efficiencies of two models on predicting irAEs in patients with advanced lung cancer.Results irAEs occurred in 10of 34patients(29.4%).The absolute value of Treg cells was lower in irAEs group[6.60(5.45,7.63)cells/μL]than that in non-irAEs group[7.85(6.88,9.85)cells/μL](U=61.500,P=0.025)before treatment,and showed no significant difference after treatment(P>0.05),and there were no significant difference in the other 11indexes between two groups both before and after treatment(P>0.05).The absolute values of Treg cells were higher in both two groups after treatment than those before treatment(P<0.05),the percentages of PD-1^(+)/

关 键 词：肺癌 外周血淋巴细胞亚型 免疫检查点抑制剂 免疫相关不良反应 

分 类 号：R734.2[医药卫生—肿瘤]