Macrophage-derived extracellular vesicles in the remodeling of the prostate cancer immune microenvironment and therapeutic resistance.

backgroundProstate cancer (PCa) is a biologically heterogeneous malignancy of the male genitourinary tract. Once the disease progresses to advanced stages, particularly castration-resistant PCa (CRPC), available treatment options become significantly limited. Although immunotherapy has demonstrated substantial clinical success in various solid tumors, its clinical benefit in PCa has been largely disappointing, mainly due to the profoundly immunosuppressive tumor microenvironment (TME). MAIN BODY: Tumor-associated macrophages (TAMs) represent a dominant immune cell population within the PCa immune microenvironment, and their functional states are closely linked to tumor progression and therapeutic responsiveness. Emerging evidence indicates that TAMs actively communicate with tumor cells and other immune subsets through the secretion of extracellular vesicles (EVs). These vesicles serve as important mediators of intercellular signaling, contributing to immune suppression, tumor progression, and the development of resistance to therapy. In this review, we comprehensively summarize recent advances in understanding the biological roles of macrophage-derived EVs (Mφ-EVs) in PCa, with particular emphasis on their involvement in immune microenvironment remodeling, tumor-promoting activities, and therapeutic resistance mechanisms.

conclusionMφ-EVs have emerged as key regulators of immunosuppression and treatment failure in PCa. A deeper understanding of their functional networks may provide novel opportunities for the development of EV-based diagnostic biomarkers and therapeutic strategies, ultimately helping to optimize immunotherapy and improve clinical outcomes in PCa.