The Research Progress of Tumor-Associated Macrophages in Prostate Cancer.

Prostate cancer (PCa) is a major global cancer burden in men, and its treatment is hindered by the immunosuppressive tumor microenvironment. In this context, PCa initially shows a favorable response to immunotherapy. However, as the disease progresses, the tumor gradually develops resistance to immunotherapy, with tumor-associated macrophages (TAMs) being key drivers. TAMs promote inflammation, angiogenesis, stromal remodeling, and immune evasion, leading to the development of castration-resistant PCa. The traditional M1/M2 dichotomy, such as proliferative-TAM (Prolif-TAM) and immunoregulatory-TAM (Reg-TAM), has been refined by single-cell RNA sequencing. In this article, we further discuss how signaling pathways regulate TAM polarization and investigate the multidimensional mechanisms by which TAMs drive PCa progression, the pathways that promote immunotherapy resistance, and the role of macrophage extracellular traps (METs) in PCa metastasis. Targeting TAMs for precision treatment of PCa is a promising therapeutic strategy. These strategies include blocking the adenosine pathway to inhibit SPP1hi-TAMs, reprogramming TAMs with immune checkpoint inhibitors (ICIs) to restore chimeric antigen receptor (CAR)-T cell activity, and novel approaches such as using microRNAs (miRNAs) and natural compounds to modulate TAM polarization. However, these treatment modalities still face challenges, including the complexity of the tumor microenvironment (TME) and TAM heterogeneity, obstacles in drug production and delivery, and toxicity management. This article aims to develop individualized targeting strategies based on the composition, functional status, and signaling dependencies of TAM subpopulations within patient tumors, with the hope of transitioning from a "one-size-fits-all" approach to precision medicine.