Crosstalk between Extracellular Vesicles and the Tumor Microenvironment: Mechanistic Insights and Therapeutic Opportunities

Extracellular vesicles (EVs) are actively secreted, membrane-enclosed nanoparticles that serve as pivotal mediators of intercellular communication. They function as key mediators of intercellular communication by transporting diverse biomolecules, including proteins, nucleic acids, and metabolites. Within the tumor microenvironment, EVs drive complex cellular crosstalk and critically regulate tumor progression by remodeling the extracellular matrix, conferring drug resistance, and reprogramming immune responses. Given their natural biocompatibility, tissue tropism, and ability to cross biological barriers, EVs have emerged as promising platforms for immunotherapy, tumor vaccines and targeted drug delivery system. Moreover, the rapid expansion of EV-based clinical trials highlights their promise in precision medicine. Concurrently, the limitations associated with EV-based therapeutic strategies are critically evaluated to inform future development. This review has also detailed the importance of single-vesicle analysis, which represents a rapidly evolving frontier in EV science. Aiming to bridge the gap between mechanistic understanding and clinical practice, this review delineates the pivotal roles of EV-mediated communication in reshaping the dynamic homeostasis of the tumor microenvironment. Moreover, we provide a critical analysis of current EV-based therapeutic pipelines and their translational challenges, offering key perspectives and theoretical support for the future of precision medicine.