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• W2967738568 endingPage "1648995" @default.
• W2967738568 startingPage "1648995" @default.
• W2967738568 abstract "Glioblastoma is the most prevalent and aggressive primary brain tumour for which total tumour lysate-pulsed dendritic cell vaccination is currently under clinical evaluation. Glioblastoma extracellular vesicles (EVs) may represent an enriched cell-free source of tumour-associated (neo-) antigens to pulse dendritic cells (DCs) for the initiation of an anti-tumour immune response. Capture and uptake of EVs by DCs could occur in a receptor-mediated and presumably glycan-dependent way, yet the glycan composition of glioblastoma EVs is unknown. Here, we set out to characterize the glycocalyx composition of glioblastoma EVs by lectin-binding ELISA and comprehensive immunogold transmission electron microscopy (immuno-TEM). The surface glycan profile of human glioblastoma cell line-derived EVs (50-200 nm) was dominated by α-2,3- and α-2,6 linked sialic acid-capped complex N-glycans and bi-antennary N-glycans. Since sialic acids can trigger immune inhibitory sialic acid-binding Ig-like lectin (Siglec) receptors, we screened for Siglec ligands on the EVs. Glioblastoma EVs showed significant binding to Siglec-9, which is highly expressed on DCs. Surprisingly, however, glioblastoma EVs lack glycans that could bind Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin (DC-SIGN, CD209), a receptor that mediates uptake and induction of CD4+ and CD8+ T cell activation. Therefore, we explored whether modification of the EV glycan surface could reduce immune inhibitory Siglec binding, while enhancing EV internalization by DCs in a DC-SIGN dependent manner. Desialylation with a pan-sialic acid hydrolase led to reduction of sialic acid expression on EVs. Moreover, insertion of a high-affinity ligand (LewisY) for DC-SIGN resulted in a four-fold increase of uptake by monocyte-derived DCs. In conclusion, we show that the glycocalyx composition of EVs is a key factor of efficient DC targeting and that modification of the EV glycocalyx potentiates EVs as anti-cancer vaccine." @default.
• W2967738568 created "2019-08-22" @default.
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• W2967738568 date "2019-08-09" @default.
• W2967738568 modified "2023-10-11" @default.
• W2967738568 title "Glycan modification of glioblastoma-derived extracellular vesicles enhances receptor-mediated targeting of dendritic cells" @default.
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• W2967738568 doi "https://doi.org/10.1080/20013078.2019.1648995" @default.
• W2967738568 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6713149" @default.
• W2967738568 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31489145" @default.
• W2967738568 hasPublicationYear "2019" @default.
• W2967738568 type Work @default.

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