Prognostic and Predictive Value of Tumor-Infiltrating Immune Cells in Urothelial Cancer of the Bladder

SIMPLE SUMMARY: There is substantial heterogeneity in the prognosis and responsiveness to registered therapies in bladder cancer. Biomarkers that can accurately predict prognosis and treatment outcome are urgently needed. Bladder cancer is considered an immunogenic tumor. In this review, we describe the available literature on the prognostic and predictive value of tumor-infiltrating immune cells and immune checkpoint expression. Several immunological markers have been associated with prognosis and treatment outcome. These markers have not yet been implemented in the clinic, likely due to the limited prognostic or predictive value of the individual markers. Future studies should, therefore, focus on combinations of biomarkers to accurately predict survival and response to treatment. The extensive overview provided here can be used to guide further biomarker research in bladder cancer. ABSTRACT: The prognosis and responsiveness to chemotherapy and checkpoint inhibitors differs substantially among patients with bladder cancer (BC). There is an unmet need for biomarkers that can accurately predict prognosis and treatment outcome. Here, we describe the available literature on the prognostic and predictive value of tumor-infiltrating immune cells in BC. Current evidence indicates that a high density of tumor-infiltrating CD8(+) T cells is a favorable prognostic factor, whereas PD-L1 expression and tumor-associated macrophages are unfavorable prognostic features. While PD-L1 expression appears unsuccessful as a biomarker for the response to checkpoint inhibitors, there are some indications that high CD8(+) T cell infiltration, low transforming growth factor-beta signaling and low densities of myeloid-derived suppressor cells are associated with response. Future studies should focus on combinations of biomarkers to accurately predict survival and response to treatment.