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

Area of Science:

• Oncology
• Immunology
• Biochemistry

Background:

• Prostate cancer (PCa) is a prevalent malignancy with high heterogeneity and an immunosuppressive tumor microenvironment (TME), leading to treatment failure.
• Castration-resistant prostate cancer (CRPC) progression, metastasis, and neuroendocrine differentiation pose significant therapeutic challenges.
• The complex interplay within the TME, involving tumor cells, stroma, and immune components, contributes to PCa's low immunogenicity.

Purpose of the Study:

• To clarify the role of monoamine oxidase (MAO) in regulating the tumor-stroma-immune network in PCa progression.
• To elucidate the impact of MAO on CD8+ T-cell infiltration and tumor-associated macrophage (TAM) polarization within the TME.
• To propose precision targeting of MAO as a strategy to overcome immunotherapy resistance in PCa.

Main Methods:

• Review of existing literature on MAO expression and function in PCa.
• Analysis of MAO's influence on immune cell infiltration and polarization in the TME.
• Exploration of MAO inhibitor-based therapeutic strategies for PCa immunotherapy.

Main Results:

• MAO, through its MAOA and MAOB isoforms, is differentially expressed in PCa cells, stromal cells, and immune cells.
• MAO activity influences the "tumor-stroma-immune" interaction network, potentially promoting PCa progression.
• MAO impacts CD8+ T-cell infiltration and TAM polarization, key factors in the TME's immunosuppressive nature.

Conclusions:

• Targeting MAO offers a promising strategy to enhance immunotherapy efficacy in PCa.
• MAO inhibitors may overcome immunotherapy resistance by modulating the TME and immune responses.
• This review provides a theoretical basis for developing novel MAO inhibitor-based interventions for effective PCa immunotherapy.