Extracellular vesicles in spine tumors: biological roles, immune modulation, and therapeutic implications

Spinal tumors, whether primary or metastatic, represent a diverse and clinically challenging group of CNS neoplasms. Recent advances in tumor biology have highlighted extracellular vesicles (EVs) as central to tumor biology. This narrative review aimed to examine the emerging role of extracellular vesicles in the pathogenesis, diagnosis, and treatment of spinal tumors and metastases, synthesizing data from preclinical and clinical studies. Tumor-derived EVs in spinal tumors modulate oncogenic signaling, angiogenesis, and immune evasion. In meningiomas and schwannomas, EVs influence tumor behavior and offer potential biomarkers such as miR-497 and e-hTERT. In astrocytomas, circulating EV-circRNAs may enable noninvasive diagnosis and monitoring. In neurofibromas, fibroblast-derived EVs enhance tumor proliferation via VEGF delivery. Metastatic spinal tumors exploit EVs to condition pre-metastatic niches and promote osteolytic or osteoblastic changes via specific miRNAs and proteins. Immune modulation by EVs, including M2 macrophage polarization and T-cell suppression further supports tumor growth. Therapeutically, EVs are being explored as vehicles for targeted drug delivery and as targets themselves via inhibition of EV biogenesis or uptake.