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- W2899788354 abstract "Glioblastoma (GBM) is the most aggressive type of primary brain cancer and carries a dire prognosis. Increasing evidence points to extracellular vesicles (EVs) as a means by which GBM tumor cells modulate the tumor microenvironment, leading to immunosuppression and disease progression. Several pharmacologic agents may inhibit EV release (fasudil, a ROCK1 inhibitor; GW4869, a Rab27B inhibitor) or block EV interactions with target cells via heparin sulfate proteoglycan (heparin, an HSPG competitive inhibitor). We sought to characterize the effects of these drugs on EVs release from GBM cells and binding to target cells. EVs released by the human GBM cell line BT116 were quantified by nanoparticle tracking in with the presence or absence of the putative release inhibitors fasudil and GW489. Compared to untreated cells, pharmacologically treated BT116 cells demonstrated modest reductions in EV release with 50uM fasudil (17%) and 10uM GW4869 (31%). We have previously demonstrated that BT116 EVs can induce immunosuppressive monocyte development including myeloid-derived suppressor cells (MDSCs) and non-classical monocytes (NCMs). Under confocal microscopy, monocytes conditioned with GBM-derived EVs demonstrated markedly reduced EV uptake in the presence of heparin than untreated cells in a dose-dependent manner (1uM-50uM heparin). In the presence of heparin, BT116 EVs induced reduced NCM formation when cocultured with normal donor-derived monocytes, but did not appear to affect MDSC differentiation. Taken together, these findings point to druggable targets in the interaction between glioblastoma-derived EVs and host immune cells. This may prove important in treating GBM-mediated immunosuppression and optimizing GBM immunotherapy." @default.
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- W2899788354 date "2018-11-01" @default.
- W2899788354 modified "2023-09-25" @default.
- W2899788354 title "IMMU-22. PHARMACOLOGICALLY TARGETING EXTRACELLULAR VESICLE-IMMUNE CELL INTERACTIONS IN GLIOBLASTOMA" @default.
- W2899788354 doi "https://doi.org/10.1093/neuonc/noy148.525" @default.
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