Targeting MAO offers a novel immunotherapeutic strategy for prostate cancer by modulating the "tumor-stroma-immune" interaction network.

Prostate cancer (PCa) is a highly prevalent malignant tumor in men, often progressing to castration-resistant prostate cancer (CRPC) and metastasis or neuroendocrine differentiation, leading to treatment failure. Its high heterogeneity and immunosuppressive tumor microenvironment (TME) are major challenges in treatment, characterized by low immunogenicity and a complex "tumor-stroma-immune" interaction network. Monoamine oxidase (MAO), a mitochondrial enzyme that degrades monoamine neurotransmitters and dietary amines via MAOA and MAOB isoforms. Studies have shown that MAOA and MAOB exhibit differential expression patterns in cancer cells, stromal cells, and immune cells, and may function cooperatively to promote PCa progression. This review clarifies how MAO influence PCa progression by regulating the "tumor-stroma-immune" interaction network, elucidate the impact of MAO on CD8+ T-cell infiltration and tumor-associated macrophages (TAMs) polarization in the TME, and proposes that precision targeting of MAO offers a stage- and cell-type-spanning strategy to surmount immunotherapy resistance in PCa. It provides a theoretical basis for developing intervention strategies based on MAO inhibitor to achieve effective immunotherapy for PCa.