BACKGROUND: The programmed death-1 (PD-1) pathway negatively regulates T-cell 
activation and has an important role in regulating antitumor host immunity. 
Monoclonal antibodies directed against PD-1 or the PD-1 ligand (PD-L1) have 
shown activity in several tumor types with preliminary data suggesting a 
relationship between PD-L1 expression and response. The aim of this study was to 
establish the frequency of PD-L1 expression in muscle-invasive bladder cancer 
and associated lymph node metastasis using immunohistochemistry and to 
investigate the feasibility of using PD-L1 expression as a biomarker to select 
patients for PD-1-directed therapy.
PATIENTS AND METHODS: Cases of radical cystectomy for muscle-invasive bladder 
cancer with no exposure to previous chemotherapy were identified and 
representative slides from archived paraffin-embedded blocks stained with 
anti-PD-L1 antibody (5H1 clone) were identified. PD-L1 positivity was defined by 
a 5% expression threshold.
RESULTS: Fifty-two radical cystectomy specimens were reviewed. PD-L1 was 
overexpressed in the tumor cells of 5/52 (9.6%) of cystectomy specimens in this 
cohort with 17/52 (32.7%) of cases showing PD-L1 overexpression in 
tumor-infiltrating immune cells. Discordance was observed between PD-L1 
expression in lymph node metastasis and the primary tumor.
CONCLUSION: Standard assays for PD-L1 expression have yet to be established. The 
observation of discordance between PD-L1 expression in metastatic sites and 
primary tumors suggests that prospective biomarker studies should aim to acquire 
material immediately before treatment initiation rather than archived tissue 
from resected specimens that might not reflect the current immune-active 
microenvironment.