Phenotypic Diversity of Immunosuppressive B Cells Associated in Urothelial Carcinoma of the Bladder

Abstract

Background

Urothelial carcinoma of the bladder presents a complex tumor microenvironment, with tumor-infiltrating B cells (TIL-Bs) playing a significant role in disease progression. Although their presence is acknowledged, the phenotypic diversity of regulatory TIL-Bs in bladder cancer remain underexplored.

Materials and Methods

In this study, we evaluated core B cell subsets and their immunosuppressive phenotypes in both peripheral blood (n=40) and bladder tumor tissues (n=40) to evaluate their relationship with disease severity.

Results

Our findings revealed that high-grade bladder tumors are enriched with B cells and their subsets, particularly transitional B cells and plasmacytes (plasmablasts and plasma cells). However, total memory B cells were reduced in the tumor microenvironment compared to non-tumor tissues. It was further revealed that the high-grade tumors demonstrated significant infiltration of regulatory B cells (Breg), with elevated levels of IL10+ and TGFβ+ Breg cells as well as IL-10+TGF-β+ dual-cytokine-secreting Breg cells, suggesting their role in fostering an immunosuppressive microenvironment. Memory B cells demonstrated the highest frequency of Breg phenotypes among the B cell subsets. Additionally, Tertiary Lymphoid Structure formation and frequency were associated with disease severity, the differentiated B cells and IL10+ Breg cell counts, emphasizing the importance of these structures in bladder cancer progression and the potential involvement in Breg cells formation.

Conclusion

This study demonstrates the enrichment of the bladder cancer tumor microenvironment with diverse B cell subsets, including functional Breg cells, which correlates with disease severity.