gms | German Medical Science

Objective: Extracellular vesicles (EVs) represent a population of lipid bilayer nanoparticles released by all cell types, including tumor cells, and have recently garnered attention as mediators of intercellular communication. Emerging evidence supports their key function in modulating the tumormicroenvironment and tumorprogression, as they are capable of horizontal transfer of pro-oncogenic cargo to recipient cells. To date, MRI-Images are the established method to monitor treatment efficacy in brain tumor patients. Given the critical need for a reliable biomarker in the therapy monitoring of glioblastoma patients, EVs are of translational interest as they harbor tumor-specific nucleic acids and proteins, transgress the blood-brain-barrier and thus may serve as a noninvasive resource for liquid biopsy. The aim of this study was to investigate the potential of circulating EVs to mirror therapy efficacy and tumorprogression.

Methods: We collected plasma samples from glioblastoma (n=40) and meningioma patients (n=25) before, as well as on the first and fourth day after, microsurgical tumorresection. Follow-up samples were obtained every 3 months. Additionally, we analyzed a group of healthy donors (n=18). EVs were isolated by Ultracentrifugation and the plasma concentration was measured by Nanoparticle Tracking Analysis (NTA). Tumor burden was measured on T1-weighted and FLAIR MRI images.

Results: Prior to surgery, the level of circulating EVs in glioblastoma and meningioma patients is elevated, distinguishing them from healthy controls (2-fold increase in meningioma, 5-fold increase in GBM; p < 0.0001). After surgery, the concentration of EVs per ml plasma decreased significantly. In the group of glioblastoma patients, the number of circulating plasma EVs dropped by a factor of 7 until the fourth day after tumor resection (p < 0.001) In meningioma patients, EV concentration decreased by a factor of 3 (p < 0.05), while it was most distinct in who grade 2. A massive drop in EVs was associated with a more radical surgical resection (p < 0.05). Interestingly, at the time of tumor recurrence, the number of circulating EVs increased again in all patients during a follow-up period of 9 months.

Conclusion: Our findings highlight the potential of circulating extracellular vesicles as a resource for monitoring treatment response of glioblastoma patients, as they seem to reflect the presence of a tumor mass and thus may assist in clinical decision making.