Extracellular Vesicles in the Tumor Microenvironment: Diverse Origins, Multifaceted Functions, and Emerging Therapeutic Opportunities

As pivotal mediators in the tumor microenvironment (TME), extracellular vesicles (EVs) orchestrate intercellular communication by transferring bioactive cargo, including proteins, lipids, and nucleic acids. These highly heterogeneous EVs can exert profoundly divergent impacts on malignant progression and clinical treatment outcomes. Beyond their intrinsic biological roles, their natural capacity for cargo transfer also supports their development as next-generation engineered delivery platforms. Furthermore, specific subtypes of EVs or those carrying particular cargo are being pursued as both therapeutic targets for modulating pathogenic signaling and as noninvasive biomarkers for diagnosis and prognosis. Although modulation of EV-mediated pathways has shown promise in preclinical models, clinical translation remains hindered by insufficient target selectivity, off-target effects, and challenges in achieving scalable, standardized manufacturing. This review synthesizes current knowledge on EV heterogeneity and their diverse functions in modulating the TME, and further outlines a framework for emerging applications in clinical diagnostics and therapeutics.