Tumor-Associated Macrophages in Bladder Cancer: Biological Role, Impact on Therapeutic Response and Perspectives for Immunotherapy

Abstract

Tumor-associated macrophages (TAMs) are one of the most abundant infiltrating immune cells of solid tumors. Despite their possible dual role, i.e., pro- or anti-tumoral, there is considerable evidence showing that the accumulation of TAMs promotes tumor progression rather than slowing it. Several strategies are being developed and clinically tested to target these cells. Bladder cancer (BCa) is one of the most common cancers, and despite heavy treatments, including immune checkpoint inhibitors (ICIs), the overall patient survival for advanced BCa is still poor. TAMs are present in bladder tumors and play a significant role in BCa development. However, few investigations have analyzed the effect of targeting TAMs in BCa. In this review, we focus on the importance of TAMs in a cancerous bladder, their association with patient outcome and treatment efficiency as well as on how current BCa treatments impact these cells. We also report different strategies used in other cancer types to develop new immunotherapeutic strategies with the aim of improving BCa management through TAMs targeting.

Remodeling the bladder tumor immune microenvironment by mycobacterial species with changes in their cell envelope composition

“…Different cell types within the myeloid cell lineage have also been shown to be involved in the regulation of immune activity in cancer ( 43 ). In agreement with previous reports ( 17 , 28 , 44 ), we found that mycobacterial treatment enhanced the infiltration of myeloid cells compared with no treatment. BCG and M. brumae treatments produced markedly different myeloid cell infiltration profiles, which were influenced by the cell envelope composition.…”

Single-cell atlases link macrophages and CD8+ T-cell subpopulations to disease progression and immunotherapy response in urothelial carcinoma

“…Indeed, both preclinical and clinical strategies targeting the tumor-promoting functions of TAMs in cancer are being developed 32 . It has been reported that M2-like macrophages impede ICIs that were based on the PD-1/PD-L1 axis 33 . Consistently, PD-L1 was highly expressed in Macro-C3 cells.…”

Clinical value of M1 macrophage-related genes identification in bladder urothelial carcinoma and in vitro validation

“…It is worth noticing that immunotherapy has shown great potential to treat MIBC and metastatic bladder cancer in the clinic ( Nair et al, 2020 ; Pfail et al, 2021 ; Zhang et al, 2022 ). Previous studies have found that macrophages exert different effects on immunotherapeutic responses in advanced cancers ( Petty and Yang, 2017 ; DeNardo and Ruffell, 2019 ; Zeng et al, 2020 ; Leblond et al, 2021 ). Sun et al ( Sun et al, 2022 ) found that the infiltration and polarization status of TAMs can predict outcomes of survival and chemotherapy benefits, as well as immunotherapy sensitivity in MIBC.…”