Decoding the metabolic‑immune crosstalk: The role of glutamine and ammonium reprogramming in prostate cancer immune...

Prostate cancer progression is typically driven by metabolic reprogramming and immune evasion, yet the interface between these processes remains incompletely understood. Dysregulated glutamine metabolism extends beyond bioenergetic support to actively shape antitumor immunity through nutrient competition and ammonium accumulation within the tumor microenvironment. Ammonium, traditionally viewed as a toxic waste product, is a critical immunosuppressive metabolite that impairs T cell function and promotes macrophage M2 polarization. The present review aimed to summarize the bidirectional crosstalk between tumor metabolism and immune cells, with emphasis on how metabolic alterations drive therapeutic resistance. While the majority of evidence supporting this axis derives from preclinical models, the present review highlights the glutamine‑ammonium axis as a promising but largely untapped therapeutic target requiring translation into clinical investigation, including combination strategies with immunotherapy.