Abstract Microglia are the resident myeloid cells of the central nervous system, and, in healthy conditions, they account for approximately 10% of the cells in the whole brain. In the presence of glioma, microglia are activated toward a pro-tumorigenic phenotype and they expand up to 40% of the total tumor mass. Although multiple evidence showed that microglia can release extracellular vesicles (EVs), little is known about the role of small EVs (sEVs) released by microglia in the context of glioma. Our hypothesis is that sEVs released by microglia play a key role in the recruitment of immune suppressive cells from the periphery, ultimately supporting tumor growth. We used two models of microglia, (i) primary resting- or tumor associated- microglia, (ii) microglia cell lines. sEVs, isolated through differential centrifugation followed by size exclusion chromatography, were characterized by ZetaView, western blot, ExoView, NanoFlow cytometry and super resolution microscopy according to MISEV2023. sEVs isolated from unconditioned medium were used as internal control in functional experiments. Microglia-sEVs were intracranially co-injected with tumor cells in C57BL/6 male and female mice. Our data showed that sEVs produced by microglia can cross the blood brain barrier and migrate to the bone marrow, where they are specifically internalized in monocyte progenitors. This led to an expansion of monocyte progenitors and monocytes. Mechanistically, we showed that sEVs activate the highly motile monocytes through the IL1a pathway. The expanded highly motile monocytes leave the bone marrow and infiltrate the tumor, where they differentiate toward immune suppressive macrophages. Altogether, this support tumor growth and the formation of an immune suppressive environment. Altogether these data identify sEVs as key player in the communication between local immune cells (microglia) and the periphery. Citation Format: Irene Bertolini, Isabela Albuja Ron, Miguel Quiralte Pulido. Microglia derived extracellular vesicles in the crosstalk between glioblastoma and the periphery abstract. In: Proceedings of the AACR Special Conference in Cancer Research: Brain Cancer; 2026 Mar 23-25; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2026;86 (6Suppl): Abstract nr PR003.
Bertolini et al. (Mon,) studied this question.