Prognostic significance of PD-L1 expression on tumor cells and tumor-infiltrating mononuclear cells in upper tract urothelial carcinoma

Bo Zhang, Wei Yu, Xueru Feng, Zheng Zhao, Yu Fan, Yisen Meng, Shuai Hu, Yun Cui, Qun He, Hong Zhang, Dong Li, Zhisong He, Liqun Zhou, Jie Jin, Wenke Han

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).