Assessment of tumoral PD-L1 expression and intratumoral CD8+ T cells in urothelial carcinoma.
OBJECTIVE
To evaluate programmed death ligand 1 (PD-L1) expression in urothelial carcinoma of the bladder in relationship with tumor-infiltrating CD8+ T cells.


METHODS
Tissue microarrays were prepared from 56 cystectomy specimens performed at our hospital (1994-2002). PD-L1 immunoexpression was assessed using the murine antihuman PD-L1 monoclonal antibody 5H1. Extent of membranous PD-L1 expression was assigned in each spot. Spots showing ≥5% expression were considered positive. Average PD-L1 expression per tumor was also calculated (5% positivity cutoff). "High CD8 density" was defined as the presence of ≥60 CD8+ intraepithelial lymphocytes per high power field in a given spot. A tumor was considered high density if ≥50% of its spots were of high density.


RESULTS
PD-L1 expression was positive in approximately 20% of tumors. None of the benign urothelium spots expressed PD-L1. High CD8 density was observed in approximately 20% of cases. CD8 density did not correlate with PD-L1 expression. Overall survival (OS) and disease-specific survival (DSS) rates were 14% and 28%, respectively (median follow-up, 31.5 months). PD-L1 expression was associated with age at cystectomy (P = .01). Remaining clinicopathologic parameters were not associated with PD-L1 expression or CD8 density. High CD8 density was associated with favorable OS (P = .02) and DSS (P = .02). The same was true when CD8 density was adjusted for demographic and clinicopathologic parameters. There was no correlation between PD-L1 expression and outcome.


CONCLUSIONS
High intratumoral CD8+ T cell density is associated with better OS and DSS in invasive urothelial carcinoma of the bladder. We found no correlation between PD-L1 expression and outcome.
Department of Pathology, Johns Hopkins University, Baltimore, MD.
Sheila F
SF
Faraj
Department of Pathology, Johns Hopkins University, Baltimore, MD.
Enrico
E
Munari
Department of Pathology, Johns Hopkins University, Baltimore, MD.
Gunes
G
Guner
Department of Pathology, Johns Hopkins University, Baltimore, MD.
Janis
J
Taube
Department of Pathology, Johns Hopkins University, Baltimore, MD.
Robert
R
Anders
Department of Pathology, Johns Hopkins University, Baltimore, MD.
Jessica
J
Hicks
Department of Pathology, Johns Hopkins University, Baltimore, MD.
Alan
A
Meeker
Department of Urology, Johns Hopkins University, Baltimore, MD; Department of Oncology, Johns Hopkins University, Baltimore, MD.
Mark
M
Schoenberg
Department of Urology, Johns Hopkins University, Baltimore, MD; Department of Oncology, Johns Hopkins University, Baltimore, MD.
Trinity
T
Bivalacqua
Department of Urology, Johns Hopkins University, Baltimore, MD; Department of Oncology, Johns Hopkins University, Baltimore, MD.
Charles
C
Drake
Department of Pathology, Johns Hopkins University, Baltimore, MD; Department of Urology, Johns Hopkins University, Baltimore, MD; Department of Oncology, Johns Hopkins University, Baltimore, MD. Electronic address: gnetto1@jhmi.edu.
George J
GJ
Netto
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000096:biosynthesis*; D018414:CD8-Positive T-Lymphocytes; D002295:Carcinoma, Transitional Cell / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D001749:Urinary Bladder Neoplasms / Q000276:immunology* / Q000378:metabolism*
D060890:B7-H1 Antigen