外周血免疫细胞对PD-1单抗治疗晚期膀胱尿路上皮癌疗效的预测作用

Prognostic effect of systemic immune cells on anti-PD-1 antibody therapy in patients with advanced urothelial bladder cancer

目的探讨晚期膀胱尿路上皮癌(urothelial bladder cancer,UBC)患者外周血免疫细胞数量对程序性死亡受体1(programmed cell death protein 1,PD-1)单抗治疗的疗效预测作用。方法回顾性分析2017年8月至2021年4月复旦大学附属中山医院接受PD-1单抗治疗的晚期UBC患者86例。收集患者临床信息、外周血免疫细胞数据及肿瘤组织PD-1/程序性死亡配体1(programmed cell death ligand 1,PD-L1)表达情况,并分析这些指标与患者生存及对PD-1单抗治疗客观反应率(objective response rate,ORR)的影响。结果TNM分期早(P=0.02)、外周血NK细胞数量高(P=0.009)、CD4^(+)T细胞占总T细胞比例高(CD4^(+)T%,P=0.009)及B淋巴细胞数量高(P=0.038)是晚期UBC患者总体生存期(overall survival,OS)良好的独立预后因子。TNM分期早(P<0.001)、外周血NK细胞水平高(P=0.043)及B淋巴细胞水平高(P=0.027)是晚期UBC患者无进展生存期(progression free survival,PFS)良好的独立预后因子。外周血B淋巴细胞数量高(P=0.011)、CD4^(+)T%高(P=0.041)和总淋巴细胞数量高(P<0.001)的患者对PD-1单抗治疗有更高的ORR。结论晚期UBC患者外周血NK细胞、B淋巴细胞及CD4^(+)T细胞可能在晚期UBC抗肿瘤免疫中发挥重要作用。患者外周血B淋巴细胞数量、CD4^(+)T%和总淋巴细胞数量影响晚期UBC患者对PD-1单抗治疗的ORR,可能参与PD-1单抗疗效发挥的进程。

Objective To explore the predictive effect of systemic immune cells on anti-programmed cell death protein 1(PD-1)antibody therapy in patients with advanced urothelial bladder cancer(UBC).Methods We retrospectively analyzed 86patients with advanced UBC who received anti-PD-1 antibody therapy.Clinical information,systemic immune cell data and tumor PD-1/programmed cell death ligand 1(PD-L1)expression status were collected.The influence of these indicators on patient survival and objective response rate(ORR)were analyzed.Results Early TNM stage(P=0.02),high systemic NK cells(P=0.009),high ratio of CD4^(+)T in T lymphocytes(CD4^(+)T%,P=0.009)and high B lymphocytes(P=0.038)were independent prognostic factors for good overall survival(OS).Patients with early TNM stage(P<0.001),high systemic NK cells(P=0.043)and high B lymphocytes(P=0.027)were independent prognostic factors of good progression free survival(PFS).Patients with high systemic B lymphocytes(P=0.011),high CD4^(+)T%(P=0.041)and high total lymphocytes(P<0.001)had higher ORR for anti-PD-1 antibody therapy.Conclusions In this study,systemic NK cells,B lymphocytes and CD4^(+)T cells of advanced UBC patients may play an important role in anti-tumor immunity.Systemic B lymphocytes,CD4^(+)T%and total lymphocytes affected the ORR of patients treated with anti-PD-1 antibody,and may be involved in the therapeutic process of anti-PD-1 treatment.