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

林志远; 卢莉莉; 陈朴; 郭剑明; 姜帅

doi:10.12025/j.issn.1008-6358.2023.20221150

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

摘要

摘要:
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。

Abstract:
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 86 patients 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.

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