Sarcoma-Derived Extracellular Vesicles: From Biology to Clinical Translation

Sarcomas constitute a heterogeneous group of rare mesenchymal malignancies encompassing soft tissue and bone sarcomas, whose histological and molecular diversity poses substantial challenges for early diagnosis, disease surveillance, and clinical management. Extracellular vesicles (EVs) are membrane-bound particles that mediate intercellular communication via delivery of bioactive cargo including proteins, nucleic acids, and lipids, and have emerged as promising analytes for minimally invasive liquid biopsy. While the biological functions and clinical value of EVs have been extensively characterized in common epithelial cancers, investigations focusing on sarcoma-derived EVs remain relatively limited and unevenly distributed across histological subtypes. Emerging evidence suggests that EV cargo can reflect molecular features of different sarcoma subtypes, including gene amplifications, fusion transcripts, miRNAs, lncRNAs, and tumor-associated proteins. This review provides an overview of current advances in sarcoma-derived EV research. We outline the classification of EV subtypes and their molecular cargo characteristics, with emphasis on features particularly relevant to sarcoma biology and biomarker development, as well as the technical principles, advantages, and limitations of EV isolation methodologies. We then focus on the roles of sarcoma-derived EVs in mediating tumor-host crosstalk, including facilitating the establishment of the pre-metastatic niche, promoting immunosuppression and immune evasion, and remodeling the tumor microenvironment. We further summarize emerging translational applications of sarcoma-derived EVs, covering their utility as circulating biomarkers for disease diagnosis, longitudinal monitoring, and treatment response assessment, as well as their potential as therapeutic targets for anti-tumor intervention. Where direct evidence in sarcoma remains limited, we distinguish findings established in sarcoma models from mechanisms extrapolated from other malignancies. Finally, we discuss current challenges to clinical translation, including small patient cohorts, lack of standardized technical protocols, and underrepresentation of rare histological subtypes. We propose that standardized EV isolation and characterization methods, larger collaborative datasets, and integration of multimodal liquid biopsy approaches will be important for advancing the clinical application of sarcoma-derived EVs and improving disease monitoring and patient management.