Assessment of tumoral PD-L1 expression and intratumoral CD8+ T cells in urothelial carcinoma

Sheila F. Faraj, Enrico Munari, Gunes Guner, Janis Taube, Robert Anders, Jessica Hicks, Alan Meeker, Mark P. Schoenberg, Trinity Bivalacqua, Charles Drake, George J. Netto

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Abstract

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

MATERIALS AND 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.

CONCLUSION: 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.

Original languageEnglish (US)
JournalUrology
Volume85
Issue number3
DOIs
StatePublished - Mar 1 2015
Externally publishedYes

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Ligands
Carcinoma
T-Lymphocytes
Cystectomy
Neoplasms
Urinary Bladder
Urothelium
Survival Rate
Cell Count
Monoclonal Antibodies
Demography
Lymphocytes

ASJC Scopus subject areas

  • Urology

Cite this

Faraj, S. F., Munari, E., Guner, G., Taube, J., Anders, R., Hicks, J., ... Netto, G. J. (2015). Assessment of tumoral PD-L1 expression and intratumoral CD8+ T cells in urothelial carcinoma. Urology, 85(3). https://doi.org/10.1016/j.urology.2014.10.020

Assessment of tumoral PD-L1 expression and intratumoral CD8+ T cells in urothelial carcinoma. / Faraj, Sheila F.; Munari, Enrico; Guner, Gunes; Taube, Janis; Anders, Robert; Hicks, Jessica; Meeker, Alan; Schoenberg, Mark P.; Bivalacqua, Trinity; Drake, Charles; Netto, George J.

In: Urology, Vol. 85, No. 3, 01.03.2015.

Research output: Contribution to journalArticle

Faraj, SF, Munari, E, Guner, G, Taube, J, Anders, R, Hicks, J, Meeker, A, Schoenberg, MP, Bivalacqua, T, Drake, C & Netto, GJ 2015, 'Assessment of tumoral PD-L1 expression and intratumoral CD8+ T cells in urothelial carcinoma', Urology, vol. 85, no. 3. https://doi.org/10.1016/j.urology.2014.10.020
Faraj, Sheila F. ; Munari, Enrico ; Guner, Gunes ; Taube, Janis ; Anders, Robert ; Hicks, Jessica ; Meeker, Alan ; Schoenberg, Mark P. ; Bivalacqua, Trinity ; Drake, Charles ; Netto, George J. / Assessment of tumoral PD-L1 expression and intratumoral CD8+ T cells in urothelial carcinoma. In: Urology. 2015 ; Vol. 85, No. 3.
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AU - Faraj, Sheila F.

AU - Munari, Enrico

AU - Guner, Gunes

AU - Taube, Janis

AU - Anders, Robert

AU - Hicks, Jessica

AU - Meeker, Alan

AU - Schoenberg, Mark P.

AU - Bivalacqua, Trinity

AU - Drake, Charles

AU - Netto, George J.

PY - 2015/3/1

Y1 - 2015/3/1

N2 - OBJECTIVE: To evaluate programmed death ligand 1 (PD-L1) expression in urothelial carcinoma of the bladder in relationship with tumor-infiltrating CD8+ T cells.MATERIALS AND 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.CONCLUSION: 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.

AB - OBJECTIVE: To evaluate programmed death ligand 1 (PD-L1) expression in urothelial carcinoma of the bladder in relationship with tumor-infiltrating CD8+ T cells.MATERIALS AND 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.CONCLUSION: 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.

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