Tumor microenvironment-mediated immune evasion and resistance in prostate cancer: mechanisms, cross-talk, and therapeutic opportunities

Prostate cancer (PCa) remains one of the leading causes of cancer-related morbidity and mortality in men worldwide, and therapeutic resistance-particularly to immunotherapy-continues to limit clinical efficacy. Mounting evidence has positioned the immunosuppressive tumor microenvironment (TME) as a core driver of disease progression and a formidable barrier to effective immune-based interventions. In this review, we present a comprehensive and multi-dimensional analysis of the cellular, stromal, and molecular constituents of the immunosuppressive TME in PCa, highlighting its significant heterogeneity and context-dependent functions. We emphasize recent breakthrough insights obtained through single-cell RNA sequencing (scRNA-seq), spatial multi-omics, and high-dimensional imaging technologies, which are redefining our understanding of tumor-immune-stromal interactions. Based on these mechanistic findings, we examine precision therapeutic strategies aimed at remodeling the TME, including combinatorial immune checkpoint blockade, metabolic reprogramming, cytokine network regulation, and advanced nanomedicine-based delivery systems. Finally, we discuss translational opportunities and future research directions, underscoring the necessity of integrating advanced omics technologies with biomarker-driven clinical trial design to enable individualized, precision interventions and improve survival outcomes for patients with PCa.