血淋巴细胞亚群对食管癌患者PD-1治疗效果的预测价值

The predictive value of peripheral blood lymphocyte subsets for PD-1 therapy in esophageal cancer patients

目的探究外周血淋巴细胞亚群与食管癌患者PD-1治疗预后之间的关系。方法选取在广东省人民医院免疫治疗的127例食管癌晚期患者,于治疗前、后分别抽外周血检测淋巴细胞亚群,同时收集患者临床资料。回顾性分析淋巴细胞亚群与PD-1治疗效果的关系。结果治疗前缓解(PR)组患者CD3+细胞(P<0.05)、CD8^(+)细胞(P<0.001)比例显著低于未缓解(PD+SD)组患者,而CD4^(+)/CD8^(+)比值(P<0.01)和NK细胞(P<0.05)比例显著高于未缓解组患者;治疗后缓解组患者外周血CD8^(+)细胞(P<0.05)比例显著低于未缓解组患者,CD19^(+)细胞(P<0.05)高于未缓解组患者;缓解组患者△CD19^(+)(P<0.05,患者治疗前后CD19^(+)差值,下同)和△CD19^(+)CD5^(+)(P<0.05)显著高于未缓解组患者。联合治疗前NK、治疗前和治疗后CD8^(+)三因素进行预测食管癌免疫治疗预后具有最高的诊断效能(AUC=0.840)、最高的约登指数(0.625)、较高的阳性预测值(0.812)和阴性预测值(0.813)。结论免疫治疗缓解组患者的高CD4^(+)/CD8^(+)比值、高比例NK细胞和低比例CD8^(+)细胞提示免疫治疗良好预后,联合治疗前、后CD8^(+)和治疗前NK三因素对免疫治疗效果具有良好的诊断价值。

Objective To explore the relationship between peripheral blood lymphocyte subsets and the prognosis of PD-1 therapy in esophageal cancer patients.Methods A total of 127 advanced esophageal cancer patients treated with immunotherapy at Guangdong Provincial People′s Hospital were selected.Peripheral blood lymphocyte subsets were measured before and after treatment,and clinical data of the patients were collected.The relationship between lymphocyte subsets and the efficacy of PD-1 therapy was retrospectively analyzed.Results Before treatment,the proportion of CD3^(+)cells(P<0.05)and CD8^(+)cells(P<0.001)in the remission group(PR)was significantly lower than that in the non-remission group(PD+SD),while the CD4^(+)/CD8^(+)ratio(P<0.01)and NK cell proportion(P<0.05)were significantly higher than those in the non-remission group.After treatment,the proportion of peripheral blood CD8^(+)cells in the remission group was significantly lower than that in the non-remission group(P<0.05),while the proportion of CD19^(+)cells was higher than that in the non-remission group(P<0.05).TheΔCD19^(+)(P<0.05,the difference value of CD19^(+)before and after treatment,the same below)andΔCD19^(+)CD5^(+)(P<0.05)in the remission group were significantly higher than those in the non-remission group.The combination of NK before treatment,CD8^(+)before and after treatment,and three factors predicted the prognosis of esophageal cancer immunotherapy with the highest diagnostic efficacy(AUC=0.840),the highest Youden index(0.625),and higher positive predictive value(0.812)and negative predictive value(0.813).Conclusion A high CD4^(+)/CD8^(+)ratio,high proportion of NK cells,and low proportion of CD8^(+)cells in the remission group indicate a good prognosis for immunotherapy.The combination of CD8^(+)before and after treatment and NK before treatment has good diagnostic value for the efficacy of immunotherapy.