子宫颈癌患者CD8^(+)FoxP3^(+)CD25^(+)T细胞亚群与帕博利珠单抗疗效的关系

Relationship between CD8^(+)FoxP3^(+)CD25^(+)T cell subsets and the therapeutic effect of pembrolizumab in patients with uterine cervical cancer

目的探讨CD8^(+)FoxP3^(+)CD25^(+) T细胞亚群与程序性死亡受体1(PD-1)抑制剂帕博利珠单抗治疗子宫颈癌效果的关系。方法回顾性分析2018年1月至2020年1月于秦皇岛市第一医院收治的105例在化疗基础上给予帕博利珠单抗治疗的子宫颈癌患者资料。采用流式细胞术检测患者外周血CD8^(+)FoxP3^(+)CD25^(+) T细胞比例。分析疗效和安全性。根据疗效将患者分为缓解组(完全缓解^(+)部分缓解)及未缓解组(疾病稳定^(+)疾病进展), 比较两组临床特征及CD8^(+)FoxP3^(+)CD25^(+) T细胞比例。采用多因素logistic回归模型分析疗效的影响因素。采用受试者工作特征(ROC)曲线分析CD8^(+)FoxP3^(+)CD25^(+) T细胞比例预测患者疗效的效能。结果全组患者的客观缓解率为17.14%(18/105), 不良反应发生率为39.05%(41/105)。缓解组中有子宫颈癌家族史患者比例低于未缓解组[5.56%(1/18)比34.48%(30/87)], 差异有统计学意义(χ^(2)=6.00, P=0.014)。105例患者治疗前后CD8^(+)FoxP3^(+)CD25^(+) T细胞比例分别为(0.83±0.21)%、(0.77±0.10)%;其中, 缓解组治疗前后CD8^(+)FoxP3^(+)CD25^(+) T细胞比例分别为(0.55±0.26)%、(0.31±0.12)%, 未缓解组分别为(0.89±0.30)%、(0.87±0.28)%;缓解组治疗后CD8^(+)FoxP3^(+)CD25^(+) T细胞比例低于治疗前(P<0.05), 未缓解组治疗前后差异无统计学意义(P>0.05), 未缓解组治疗前后CD8^(+)FoxP3^(+)CD25^(+) T细胞比例均高于缓解组(均P<0.001)。治疗前CD8^(+)FoxP3^(+)CD25^(+) T细胞比例高于治疗前全组均值及治疗后CD8^(+)FoxP3^(+)CD25^(+) T细胞比例高于治疗后全组均值为疾病缓解的独立危险因素(OR=2.542, 95%CI 1.649~3.918, P<0.001;OR=2.936, 95%CI 2.154~4.002, P<0.001)。ROC曲线分析显示, 治疗前CD8^(+)FoxP3^(+)CD25^(+) T细胞比例预测疾病缓解的曲线下面积为0.720, 最佳临界值为0.77%, 灵敏度和特异度分别为77.78%和70.11%。结论早期检测CD8^(+)FoxP3^(+)CD25^(+) T细胞比例有助于预测PD-1抑制剂帕博利珠单抗治疗子宫颈癌的效果。

Objective To investigate the relationship between CD8^(+)FoxP3^(+)CD25^(+)T cell subsets and the therapeutic effect of programmed death receptor 1(PD-1)inhibitor pembrolizumab in treatment of uterine cervical cancer.Methods The data of 105 patients with uterine cervical cancer who received pemblizumab therapy based on chemotherapy in the First Hospital of Qinhuangdao from January 2018 to January 2020 were retrospectively analyzed.Flow cytometry was used to detect the ratio of CD8^(+)FoxP3^(+)CD25^(+)T cell in peripheral blood of patients.The efficacy and safety were analyzed.According to the efficacy,all patients were divided into remission group(complete remission^(+)partial remission)and non-remission group(stable disease^(+)progressive disease).The clinical characteristics and CD8^(+)FoxP3^(+)CD25^(+)T cell ratio of the two groups were compared.Multivariate logistic regression model was used to analyze the influencing factors for the efficacy.The efficacy of CD8^(+)FoxP3^(+)CD25^(+)T cell ratio predicting the therapeutic effect of patients was analyzed by using receiver operating characteristic(ROC)curve.Results The objective remission rate of all patients was 17.14%(18/105),and the incidence of adverse reaction was 39.05%(41/105).The proportion of patients with a family history of cervical cancer in the remission group was lower than that than in the non-remission group[5.56%(1/18)vs.34.48%(30/87)],and the difference was statistically significant(χ^(2)=6.00,P=0.014).The proportion of CD8^(+)FoxP3^(+)CD25^(+)T cell of 105 patients before and after treatment was(0.83±0.21)%and(0.77±0.10)%,respectively;the proportion of CD8^(+)FoxP3^(+)CD25^(+)T cell before and after treatment in the remission group was(0.55±0.26)%,(0.31±0.12)%,respectively;the proportion of CD8^(+)FoxP3^(+)CD25^(+)T cell before and after treatment in the non-remission group was(0.89±0.30)%,(0.87±0.28)%,respectively.The proportion of CD8^(+)FoxP3^(+)CD25^(+)T cell after treatment in the remission group was lower than that before treatment(P<0.05);there was no statistically significant difference in the proportion of CD8^(+)FoxP3^(+)CD25^(+)T cell before and after treatment in the non-remission group(P>0.05).The proportion of CD8^(+)FoxP3^(+)CD25^(+)T cell before and after treatment in the non-remission group was higher than that in the remission group(all P<0.001).The proportion of CD8^(+)FoxP3^(+)CD25^(+)T cell higher than the mean value of both groups before treatment and the proportion of CD8^(+)FoxP3^(+)CD25^(+)T cell higher than the mean value of both groups after treatment were independent risk factor of disease remission(OR=2.542,95%CI 1.649-3.918,P<0.001;OR=2.936,95%CI 2.154-4.002,P<0.001).ROC curve analysis showed that the area under the curve of CD8^(+)FoxP3^(+)CD25^(+)T cell ratio predicting the disease remission before treatment was 0.720,and its best cut-off value was 0.77%,the senfitivity was 77.78%,the specificity was 70.11%.Conclusions Early detection of CD8^(+)FoxP3^(+)CD25^(+)T cell ratio helps to predict the effect of PD-1 inhibitor pembrolizumab therapy for uterine cervical cancer.