title: Changes in Immunogenicity during the Development of Urinary Bladder Cancer: A Preliminary Study.
abstract: In the present study, we evaluated tumor-infiltrating lymphocytes (TILs) and blood regulatory T lymphocyte (Tregs, CD4+/CD25+/FoxP3+) expression in bladder cancer patients. The number of CD4+, CD8+, CD25+, FoxP3+ and CD20+ TILs was analyzed in association with clinico-pathomorphological features. In more advanced metastasizing tumors, showing non-classic differentiation (ND) and a more aggressive tissue invasion type (TIT), the number of TILs decreased. A low number of CD4+ TILs was associated with poor prognosis. Similarly, Treg frequency before surgery and after surgical treatment was significantly lower in more advanced tumors. The changes in TILs, as well as of local and systemic Tregs, were accompanied by changes in the histological phenotype of urothelial carcinoma regarding pT stage, NDs, TIT, and clinical outcomes. The number of TILs and the frequency of blood Tregs (indicators of antitumor response) may be essential for choosing an immunotherapy that is adjusted to the immune status according to the phase of tumor growth. Moreover, a significant reduction in the number of CD4+ and CD8+ TILs with the development of NDs in more advanced tumors may be associated with lower tumor immunogenicity, resulting in immune tolerance towards tumor tissue. These observations and the tendency of urothelial bladder carcinoma to undergo NDs in a heterogeneous manner during tumor progression suggest complex interactions between bladder cancer immunogenicity and stages of tumor progression.
authors.affiliation: Department of Tumour Pathology and Pathomorphology, Faculty of Health Sciences, Nicolaus Copernicus University Collegium Medicum in Bydgoszcz, Romanowska Street 2, Bydgoszcz 85-796, Poland. jozwickiw@co.bydgoszcz.pl.|Department of Tumour Pathology and Pathomorphology, Oncology Centre-Prof. Franciszek Łukaszczyk Memorial Hospital, Romanowska Street 2, Bydgoszcz 85-796, Poland. jozwickiw@co.bydgoszcz.pl.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Jóźwicki
authors.affiliation: Department of Tumour Pathology and Pathomorphology, Faculty of Health Sciences, Nicolaus Copernicus University Collegium Medicum in Bydgoszcz, Romanowska Street 2, Bydgoszcz 85-796, Poland. anna.brozyna@cm.umk.pl.|Department of Tumour Pathology and Pathomorphology, Oncology Centre-Prof. Franciszek Łukaszczyk Memorial Hospital, Romanowska Street 2, Bydgoszcz 85-796, Poland. anna.brozyna@cm.umk.pl.
authors.forename: Anna A
authors.initials: AA
authors.lastname: Brożyna
authors.affiliation: Department of Urology, Oncology Centre-Prof. Franciszek Łukaszczyk Memorial Hospital, Romanowska Street 2, Bydgoszcz 85-796, Poland. siekieraj@co.bydgoszcz.pl.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Siekiera
authors.affiliation: Departments of Dermatology and Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. aslominski@uabmc.edu.|Laboratory Service of the VA Medical Center, 700 South 19th Street, Birmingham, AL 35233, USA. aslominski@uabmc.edu.
authors.forename: Andrzej T
authors.initials: AT
authors.lastname: Slominski
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002277:Carcinoma / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D001749:Urinary Bladder Neoplasms / Q000276:immunology* / Q000473:pathology
keywords: Tregs; non-classic differentiation number (NDN); tissue invasion type; tumor-infiltrating lymphocytes (TILs); urinary bladder cancer