Tertiary Lymphoid Structures Associate with Tumour Stage in Urothelial Bladder Cancer

Urothelial bladder cancer (UBC) is a highly prevalent disease in North America, however its optimal management remains elusive. The contribution of B cell associated responses is poorly understood in bladder cancer. Lymphoid neogenesis is a hallmark of an active immune response at tumor sites that sometimes leads to formation of tertiary lymphoid structures (TLS) that resemble germinal centers formed in secondary lymphoid organs.

This study was conducted with an aim to investigate the presence and characteristics of TLS in UBC with a focus to compare and contrast the TLS formation in treatment naive low grade non-muscle invasive (NMIBC) and muscle invasive bladder cancers (MIBC).

The study cohort consisted of transurethral bladder resection tumour (TURBT) specimens from 28 patients. Sections showing lymphoid aggregates in hematoxylin and eosin (H&E) stained TURBT specimens were further subjected to multi-color immunohistochemistry using immune cell markers specific to CD20⁺ B cells, CD3⁺ and CD8⁺ T cells, PNAd⁺ high endothelial venules, CD208⁺ mature dendritic cells, CD21⁺ follicular dendritic cells to confirm the hallmarks of classical germinal centers.

Our pilot study investigating the presence of TLS in bladder cancer patients is the first to demonstrate that well-formed TLS are more common in aggressive high grade MIBC tumors compared to low grade NIMBC.

These novel findings suggest B cell mediated anti-tumour humoral immune responses in bladder cancer progression.