Unconventional T cells in urological cancers: catch them if you can.

Unconventional T cells - including γδ T cells, mucosal-associated invariant T cells, natural killer T cells, double-positive (CD4⁺CD8⁺) and double-negative (CD4- CD8-) T lymphocytes - are an underexplored component of immune surveillance in urological cancers. Unlike conventional αβ T cells, these populations recognize mainly non-peptidic antigens independently of classic major histocompatibility complex restriction, enabling rapid responses to cellular stress, microbial cues and metabolic dysregulation within tissues and the tumour microenvironment. Emerging evidence suggests that each subset exhibits context-dependent behaviour across prostate cancer, bladder cancer and renal cell carcinoma, ranging from cytotoxic to immunoregulatory. Together, these unconventional T cell subsets offer a foundation for novel diagnostic and therapeutic strategies. Combination approaches currently in clinical trials that integrate checkpoint blockade, adoptive cell transfer or Bacillus Calmette-Guérin-based immunotherapy could be guided by emerging insights into how these cells recognize or are shaped by tumour cells. Research in mechanistic and translational studies involving unconventional T cells is gaining momentum and could ultimately redefine immune targeting in urological cancers.