The prognostic role of tumor-infiltrating lymphocytes in urothelial carcinoma of bladder: A systematic review and meta-analysis

Abstract

Background: Tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment are associated with different prognosis in various malignancies. However, their prognostic impact remains controversial in urothelial carcinoma of bladder (UCB). In this systematic review and meta-analysis, we aimed to investigate the prognostic value of TILs in UCB patients.Methods: A systematic review and meta-analysis was performed using Pubmed, Embase and Cochrane Library. Studies were eligible if they investigated the prognostic value of CD3+, CD4+, CD8+, Foxp3+ lymphocytes or TILs in UCB patients, by time-to-event survival analysis. All studies were appraised for risk of bias using the Quality and Prognosis Studies (QUIPS) criteria. Hazard rations (HRs) with their 95% confidence interval (CIs) from each study were used to generate pooled HRs. Results: A total of 14 studies assessing the impact of TILs on prognostic outcomes in UCB patients were included in final analysis. The pooled analysis indicated a favorable role of CD3+ TILs (HR 0.74 (95% CI 0.62-0.88) for overall survival) and CD8+ TILs (HR 0.46 (95% CI 0.28-0.74) for OS) in the clinical outcomes of UCB, while Foxp3+ TILs were associated with worse survival (HR 2.21 (95% CI 1.47-3.32) for recurrence-free survival). Conclusions: This systematic review and meta-analysis confirmed the favorable prognostic impact of CD3+ and CD8+ tumor-infiltrating T cells in UCB patients and found the association between Foxp3+ TILs and worse survival. Future studies using large cohorts and standardized methodology with regard to tumor subsites, stages and treatment modalities are needed to incorporate TILs with clinical practice.