Expression and prognostic value of PD-L1 in non-schistosoma-associated urinary bladder squamous cell carcinoma

Abstract

Background: Non-schistosoma-associated urinary bladder squamous cell carcinoma (SqCC) has low incidence and is associated with chronic inflammation. Due to its unique etiology and pathology, expression of programmed cell death ligand 1 (PD-L1) in SqCC could be different from that of urothelial carcinoma, which may contribute to different responses to immunotherapy. In this study, we intended to explore the expression profile and prognostic value of PD-L1 in non-schistosoma-associated urinary bladder SqCC under the consideration of tumor-infiltrating lymphocytes’ (TILs) density.

Methods: We conducted a retrospective study to review 604 bladder cancer patients who received radical cystectomy (RC) from 2009 to 2013 in Peking University First Hospital. We enrolled 67 bladder SqCC patients in total, including pure SqCC (n=19) and mixed SqCC (n=48, with urothelial carcinoma). PD-L1 protein expression and TILs density were evaluated by immunohistochemistry.

Results: Nine female and 58 male patients (median age 67.4 years) were enrolled in the present study. There were 15 stage T1-2 patients and 52 stage T3-4 patients. 27 patients had N1-2 lymph node metastasis. Overall, 61.2% cases were PD-L1-positive. Dense TILs coincided with higher PD-L1 expression rate. Median survival time of PD-L1 positive cases was significantly higher than negative cases (P=0.026). During multivariate analysis, positive PD-L1 expression and dense TILs were independent protective factors affecting overall survival (OS, PD-L1: P=0.022; TILs: P=0.010) and progression free survival (PFS, PD-L1: P=0.018; TILs: P=0.009).

Conclusions: PD-L1 expression and dense TILs were frequently detected in urinary bladder SqCC tumors. Positive PD-L1 expression and dense TILs were correlated with better survival outcomes in non-schistosoma-associated urinary bladder SqCC. The immunotherapy targeting PD-L1 might be helpful to bladder SqCC patients.

Keywords: Bladder cancer; programmed death ligand-1; squamous cell carcinoma (SqCC); survival; tumor-infiltrating lymphocytes (TILs).