From mechanisms to therapy: the role of tertiary lymphoid structures in bladder cancer

Tertiary lymphoid structures (TLS) are ectopic lymphoid tissues that form within the tumor microenvironment (TME) and play a crucial role in anti-tumor immunity. In recent years, their presence, formation mechanisms, and functional significance in bladder cancer have attracted considerable attention. This review comprehensively examines the mechanisms underlying TLS induction in bladder cancer, their role in mediating anti-tumor immunity, their correlation with favorable clinical prognosis, and their emerging potential as therapeutic targets. Current evidence suggests that high TLS density, particularly in mature forms, is associated with prolonged patient survival and improved response to immunotherapy. TLS formation is driven by a complex network of chemokines, cytokines, and specific immune cells. By providing a structured niche for the activation, clonal expansion, and effector functions of resident T/B cells, TLS exert potent anti-tumor effects. Therefore, strategies aimed at inducing or enhancing functional TLS represent a promising frontier in bladder cancer immunotherapy, although several challenges remain for successful clinical translation.