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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月26日

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  • Mingfeng Li,
  • Louis Boafo Kwantwi,
  • Cuimei Wang,
  • Qin Xiao

摘要

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.