Zhang Bo, Yu Wei, Feng Xueru, Zhao Zheng, Fan Yu, Meng Yisen, Hu Shuai, Cui Yun, He Qun, Zhang Hong, Li Dong, He Zhisong, Zhou Liqun, Jin Jie, Han Wenke
Department of Urology, Peking University First Hospital, Institute of Urology, Peking University, National Urological Cancer Center, No. 8 Xi Shi Ku St., West District, Beijing, People's Republic of China.
Department of Geriatrics, Peking University First Hospital, No. 8 Xi Shi Ku St., West District, Beijing, People's Republic of China.
Med Oncol. 2017 May;34(5):94. doi: 10.1007/s12032-017-0941-2. Epub 2017 Apr 13.
Immunotherapy targeting the programmed death-1 (PD-1) receptor/PD-1 ligand (PD-L1) pathway has shown promising results in several malignancies. However, the prognostic significance of PD-L1 expression remains unknown in patients with upper tract urothelial carcinoma (UTUC). This study aimed to evaluate PD-L1 expression and its association with clinicopathological characteristics and oncological outcomes in UTUC patients. PD-L1 expression on tumor cells and tumor-infiltrating mononuclear cells (TIMCs), and E-cadherin and N-cadherin expression on tumor cells were assessed by immunohistochemistry in a cohort of 162 patients with UTUC. Associations of PD-L1 expression on tumor cells and TIMCs with clinicopathological characteristics and cancer-specific survival (CSS) were evaluated. Out of 162 patients, 20 (12.3%) and 35 (21.6%) had positive PD-L1 expression on tumor cells and TIMCs, respectively. Decreased E-cadherin expression was associated with PD-L1 positivity on tumor cells (P = 0.048) and PD-L1 negativity on TIMCs (P = 0.033). PD-L1 expression on tumor cells was higher in patients with preoperative chronic kidney disease (CKD) stage 4-5 than in those with no CKD or CKD stage 1-3 (P = 0.011). PD-L1 was differentially expressed in tumor cells and TIMCs in UTUC. Multivariate analyses revealed that PD-L1 expression on tumor cells independently predicted shorter CSS (P = 0.012), whereas PD-L1 expression on TIMCs independently predicted longer CSS (P = 0.034).
靶向程序性死亡-1（PD-1）受体/PD-1配体（PD-L1）通路的免疫疗法在多种恶性肿瘤中已显示出有前景的结果。然而，在上尿路尿路上皮癌（UTUC）患者中，PD-L1表达的预后意义仍不清楚。本研究旨在评估UTUC患者中PD-L1的表达及其与临床病理特征和肿瘤学结局的关联。通过免疫组织化学对162例UTUC患者队列中的肿瘤细胞和肿瘤浸润单核细胞（TIMC）上的PD-L1表达以及肿瘤细胞上的E-钙黏蛋白和N-钙黏蛋白表达进行评估。评估肿瘤细胞和TIMC上PD-L1表达与临床病理特征和癌症特异性生存（CSS）的关联。在162例患者中，分别有20例（12.3%）和35例（21.6%）肿瘤细胞和TIMC上的PD-L1表达呈阳性。E-钙黏蛋白表达降低与肿瘤细胞上的PD-L1阳性（P = 0.048）和TIMC上的PD-L1阴性（P = 0.033）相关。术前慢性肾脏病（CKD）4 - 5期患者肿瘤细胞上的PD-L1表达高于无CKD或CKD 1 - 3期患者（P = 0.011）。UTUC中肿瘤细胞和TIMC上的PD-L1表达存在差异。多因素分析显示，肿瘤细胞上的PD-L1表达独立预测较短的CSS（P = 0.012），而TIMC上的PD-L1表达独立预测较长的CSS（P = 0.034）。
