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

Abstract

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.

• Authors: 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
• Journal: Human pathology (Hum Pathol) Vol. 89 Pg. 24-32 (07 2019) ISSN: 1532-8392 [Electronic] United States
• PMID: 31026471 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• B7-H1 Antigen
• Biomarkers, Tumor
• CD274 protein, human
• FOXP3 protein, human
• Forkhead Transcription Factors

Topics

• Aged
• Aged, 80 and over
• B7-H1 Antigen (immunology)
• Biomarkers, Tumor (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Carcinoma, Transitional Cell (immunology, pathology)
• Female
• Forkhead Transcription Factors (immunology)
• Humans
• Lymphocytes, Tumor-Infiltrating (immunology)
• Male
• Middle Aged
• Neoplasm Invasiveness
• Tumor Microenvironment (immunology)
• Urinary Bladder Neoplasms (immunology, pathology)