Tumor immune microenvironment in non–muscle-invasive urothelial carcinoma of the bladder

Marie Lisa Eich, Alcides Chaux, Gunes Guner, Diana Taheri, Maria Angélica Mendoza Rodriguez, Maria Del Carmen Rodriguez Peña, Alexander S. Baras, Noah M. Hahn, Charles Drake, Rajni Sharma, Trinity J. Bivalacqua, Katayoon Rezaei, George J. Netto

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Immunotherapy has gained significance in a variety of tumor types including advanced urothelial carcinoma. Noninvasive urothelial lesions have been treated with intravesical Bacillus-Calmette-Guerin (BCG) for decades. Given treatment failure in a subset of these tumors, ongoing clinical trials investigating the role of checkpoint inhibitors are actively pursued in this group of patients. The present study aims to delineate PD-L1, CD8, and FOXP3 expression in tumor microenvironment in non–muscle-invasive urothelial carcinoma samples obtained via sequential biopsies and to assess its potential role in predicting disease outcome. Cases with >1% and> 5% PD-L1 expression in tumor cells showed lower relative risk (RR) to recur at any subsequent biopsy compared with those with lower PD-L1 expression (RRs, 0.83 [P = .009] and 0.81 [P = .03], respectively). Cases with higher expression of FOXP3 in peritumoral lymphocytes were at lower risk for tumor grade progression at any biopsy (RR, 0.2; P = .02). Tumors with FOXP3/CD8 expression ratio of >1 in intratumoral lymphocytes had lower risk of grade progression (RR, 0.28; P = .04). Although higher number of FOXP3-, CD8-, and PD-L1–positive lymphocytes were encountered after BCG treatment, the findings did not reach statistical significance. In patients without BCG treatment, PD-L1 expression in tumor cells and peritumoral lymphocytes varied across serial biopsies, suggesting the need for additional approaches to assess eligibility for immunotherapy in non–muscle-invasive urothelial carcinoma patients.

Original languageEnglish (US)
Pages (from-to)24-32
Number of pages9
JournalHuman pathology
StatePublished - Jul 2019


  • Bladder
  • CD8
  • FOXP3
  • Ki-67
  • Non-invasive urothelial carcinoma
  • PD-L1

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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