Effective Treatments for Bladder Cancer Affecting CXCL9/CXCL10/CXCL11/ CXCR3 Axis: A Review

Abstract

Bladder cancer (BC) originates mainly from the epithelial compartment of the bladder, which is defined as transitional cell carcinoma or urothelial cell carcinoma. About 70% of patients with BC will survive five years from diagnosis. Previous studies revealed that the immune system and its mediators, particularly chemokines, play a crucial role in modulating responses against BC. Chemokines, which serve as chemoattractants for leukocytes, are small proteins that can initiate inflammatory and anti-inflammatory immune responses and also are associated with many aspects of both regulation and progression of mentioned responses. Additionally, these immune mediators can interfere with the other tumor-related processes, including tumor proliferation, neovascularization, and metastases. Among these chemokines, CXC chemokines, including CXCL9, CXCL10, and CXCL11, are recognized as the main ligands of C-X-C motif chemokine receptor 3 (CXCR3) and contribute to related immune responses after therapeutic strategies for BC. Evidence suggests that the production of these chemokines can have two important implications. First, these mediators can trigger the accumulation of CD8+ T cells that can contribute to the elimination of the tumor. Secondly, the production of these chemokines by tumor tissue may trigger the migration and activation of immune cells including myeloid-derived suppressor cells and regulatory T cells, which act in favor of the tumor and its progress. Therefore, in this review, we describe the latest therapeutic approaches based on targeting this axis's components and subsequent immune phenomenon.