Chiang Pei-Jhang, Xu Ting, Cha Tai-Lung, Tsai Yi-Ta, Liu Shu-Yu, Wu Sheng-Tang, Meng En, Tsao Chih-Wei, Kao Chien-Chang, Chen Chin-Li, Sun Guang-Huan, Yu Dah-Shyong, Chang Sun-Yran, Yang Ming-Hsin
Division of Urology, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan.
Graduate School of Medical Sciences, National Defense Medical Center, Taipei 11490, Taiwan.
Biology (Basel). 2021 Jul 16;10(7):674. doi: 10.3390/biology10070674.
Programmed cell death ligand 1 (PD-L1) inhibitors are commonly used in treating advanced-stage urothelial carcinoma (UC). Therefore, this study evaluated the relationship between PD-L1 expression in circulating tumor cells (CTCs) and treatment response to PD-L1 inhibitors using blood samples collected from patients with UC ( = 23). Subsequently, PD-L1 expression and its clinical correlation were analyzed. All patients had CTCs before PD-L1 inhibitory treatment, of which 15 had PD-L1-positive CTCs. However, PD-L1-positive expression in CTCs was not correlated with PD-L1 expression in tumor biopsy samples. Patients with PD-L1-positive CTCs had better disease control (DC) rates than those without PD-L1-positive CTCs. Moreover, changes in the proportion of PD-L1-positive CTCs were associated with disease outcomes. Furthermore, the PD-L1-positive CTC count in 9 of 11 patients who achieved DC had significantly decreased ( = 0.01). In four patients with progressive disease, this was higher or did not change. PD-L1-positive CTCs at baseline could be used as a biomarker to identify patients suitable for PD-L1 blockade therapy. Dynamic changes in PD-L1-positive CTCs during the course of treatment are predictive factors of immunotherapy response and prognostic factors of disease control. Hence, PD-L1-positive CTCs could be employed as a real-time molecular biomarker for individualized immunotherapy.
程序性细胞死亡配体1（PD-L1）抑制剂常用于治疗晚期尿路上皮癌（UC）。因此，本研究利用从UC患者（n = 23）采集的血样，评估循环肿瘤细胞（CTC）中PD-L1表达与对PD-L1抑制剂治疗反应之间的关系。随后，分析了PD-L1表达及其临床相关性。所有患者在接受PD-L1抑制治疗前均有CTC，其中15例患者的CTC为PD-L1阳性。然而，CTC中的PD-L1阳性表达与肿瘤活检样本中的PD-L1表达无关。PD-L1阳性CTC的患者比没有PD-L1阳性CTC的患者具有更好的疾病控制（DC）率。此外，PD-L1阳性CTC比例的变化与疾病转归相关。此外，在11例实现疾病控制的患者中，有9例患者的PD-L1阳性CTC计数显著下降（P = 0.01）。在4例疾病进展的患者中，该计数较高或未发生变化。基线时的PD-L1阳性CTC可作为一种生物标志物，用于识别适合PD-L1阻断治疗的患者。治疗过程中PD-L1阳性CTC的动态变化是免疫治疗反应的预测因素和疾病控制的预后因素。因此，PD-L1阳性CTC可作为个体化免疫治疗的实时分子生物标志物。
