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bioRxiv · 10.64898/2026.07.24.740563

Sialyl-Tn-positive tumour-derived extracellular vesicles impair dendritic cell function via horizontal transfer of glycans

Silva, Z. C.·Andre, N. D.·Sharma, S.·Vieira, M. S.·de Oliveira, B. R.·Videira, P. A.
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Abstract

The sialyl-Tn (STn) glycan antigen is aberrantly expressed in a subset of triple-negative breast cancer (TNBC) and is associated with poor prognosis and immunosuppressive microenvironment. Tumour-derived extracellular vesicles (TDEVs) are emerging regulators of immune escape however the role of glycan-mediated mechanisms remains elusive. Aberrant glycosylation is a hallmark of cancer that extends to TDEVs, yet how tumour-associated glycans within EV cargo modulate cell function remains poorly understood. Here we used engineered MDA-MB-231 TNBC cells to overexpress the glycosyltransferase ST6GalNAc-I, generating STn-positive cells whose EVs were enriched in STn (STn+ EV). The STn+ EVs impaired the maturation of monocyte-derived dendritic cells (DCs), reduced antigen presentation, and diminished CD4{square} and CD8{square} T cell priming, alongside the expansion of regulatory T cells. DCs co-cultured with STn{square} EVs display STn at their cell surface. Notably, STn+ EVs transferred both STn antigen and the ST6GalNAc-I to recipient DCs. Enzymatic removal of terminal sialic acids from STn{square} EVs reversed the immunosuppressive effects, confirming the STn{square}dependent nature of DC dysfunction. These findings add STn to the extensive list of components of EVs molecular cargo that play a role in immune suppression and may contribute for developing precision medicine approaches in oncology.

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Silva, Z. C., Andre, N. D., Sharma, S., Vieira, M. S., de Oliveira, B. R., Videira, P. A.. 2026-07-26. Sialyl-Tn-positive tumour-derived extracellular vesicles impair dendritic cell function via horizontal transfer of glycans. https://doi.org/10.64898/2026.07.24.740563

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