Balcik, Onur YazdanYilmaz, Fatih2026-01-242026-01-2420251078-14391873-2496https://doi.org/10.1016/j.urolonc.2024.11.017https://hdl.handle.net/20.500.12868/5808Objective: Bladder carcinoma (BC) is a common type of cancer. Approximately 20% of BC patients have non-muscle invasive bladder cancer (NMIBC). Despite adequate BCG treatment, recurrence occurs in approximately 40% of the patients. There is no adequate prognostic marker for recurrence in a group of patients. Forkhead box P3 (FOXP3) is a regulatory T cell marker that sometimes exhibits anti- tumoral effects and can be used as a tumor marker. T-cell immunoglobulin and mucin domain 3 (TIM-3) is an immune checkpoint inhibitor of T cells. Tertiary lymphoid structures (TLS) increase malignancy and inflammation in non-lymphoid organs. Therefore, we aimed to evaluate the prognostic value of FOXP3, TIM-3, and TLS in patients with NMIBC. Methods: Patients with pathologically confirmed NMIBC were included in this study. Stromal and intraepithelial cells were evaluated separately using immunohistochemistry, and FOXP3, TIM-3, TLS, FOXP3/TLS, and TIM-3/TLS were calculated and noted. The cutoff value was determined using ROC analysis. Recurrence-free survival (RFS) and overall survival (OS) were evaluated using univariate and multivariate Cox proportional hazard analyses. Results: The study included ninety-six patients. FOXP3/TLS high group had a better RFS than FOXP3/TLS low group (P = 0.001; HR, 0.079; 95% CI, 0.019-0.337). This was also significant in the multivariate analysis (P = 0.018; HR, 0.125; 95% CI, 0.022-0.705). In the group receiving BCG, FOXP3/TLS, FOXP3-TLS, TIM-3-TLS and TIM-3/TLS elevation were lower in patients with relapse than in patients without relapse and were statistically significant. Combined TIM-3 and FOXP3 elevation was found to be good prognostic regardless of whether it was found in intraepithelial, stromal or TLS. Conclusion: FOXP3/TLS elevation is a good prognostic and predictive marker in all non-muscle invasive bladder cancer cases and in the subgroup receiving BCG. Elevation of FOXP3-TLS, TIM-3-TLS, and TIM-3/TLS is associated with longer RFS in patients receiving BCG. Combined TIM-3 and FOXP3 elevation is indicative of a low recurrence rate in NMIBC. (c) 2024 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.eninfo:eu-repo/semantics/closedAccessFOXP3TIM-3TLSRFSTregArticle10.1016/j.urolonc.2024.11.0174342.68E+112.6799999999999999147E+28396681052-s2.0-85211716283Q1WOS:001445229000001Q2