CD4, CD20 and PD-L1 as a marker of recurrence in non-muscle invasive bladder cancer

Abstract

Introduction A tumor microenvironment plays an important role in bladder cancer development as well as in a treatment response. Purpose The aim of the study is to assess how the components of the microenvironment, in terms of cells, potentially affect tumor recurrence as well as to find the potential biomarkers for immunotherapy in NMIBC. Methods The study group consisted of 55 patients with primary NMIBC. Immunohistochemistry was performed on sections of primary papillary urothelial carcinoma of the bladder removed during transurethral resection of the tumor. Cox proportional hazard multiple regression analysis was performed to characterize tumors with the highest probability of an unfavorable outcome. Results The expression of analyzed variables was found in 90% of the examined tissues. Multivariate analysis confirmed that the CD4 (HR 1.19, 95% CI 1.07-1.32, p = 0.001), CD20 (HR 0.9, 95% CI 0.84-0.97, p = 0.008) and PD-L1 expressed on tumor cells (HR 0.05, 95% CI 0.008-0.29, p = 0.01) were independently associated with the risk of recurrence of bladder cancer. Patients with weak CD4+ cells (< 4,6%) infiltration and severe CD20+ infiltration (>10%) belong to the group with a lower risk of recurrence. The cancer in this group frequently recurs also after 12 months (p=0.0005). Conclusions The evaluation of CD4+ and CD20+ cells in the tumor microenvironment, in addition to PD-L1 on tumor cells, facilitates determination of a group of patients with a low risk of the recurrence that could also be recognized after 12 months following the primary tumor resection.