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  • Glioblastomas exploit truncated O-linked glycans for local and distant immune modulation via the macrophage galactose-type lectin.

Glioblastomas exploit truncated O-linked glycans for local and distant immune modulation via the macrophage galactose-type lectin.

Proceedings of the National Academy of Sciences of the United States of America (2020-02-06)
Sophie A Dusoswa, Jan Verhoeff, Erik Abels, Santiago P Méndez-Huergo, Diego O Croci, Lisan H Kuijper, Elena de Miguel, Valerie M C J Wouters, Myron G Best, Ernesto Rodriguez, Lenneke A M Cornelissen, Sandra J van Vliet, Pieter Wesseling, Xandra O Breakefield, David P Noske, Thomas Würdinger, Marike L D Broekman, Gabriel A Rabinovich, Yvette van Kooyk, Juan J Garcia-Vallejo
ABSTRACT

Glioblastoma is the most aggressive brain malignancy, for which immunotherapy has failed to prolong survival. Glioblastoma-associated immune infiltrates are dominated by tumor-associated macrophages and microglia (TAMs), which are key mediators of immune suppression and resistance to immunotherapy. We and others demonstrated aberrant expression of glycans in different cancer types. These tumor-associated glycans trigger inhibitory signaling in TAMs through glycan-binding receptors. We investigated the glioblastoma glycocalyx as a tumor-intrinsic immune suppressor. We detected increased expression of both tumor-associated truncated O-linked glycans and their receptor, macrophage galactose-type lectin (MGL), on CD163+ TAMs in glioblastoma patient-derived tumor tissues. In an immunocompetent orthotopic glioma mouse model overexpressing truncated O-linked glycans (MGL ligands), high-dimensional mass cytometry revealed a wide heterogeneity of infiltrating myeloid cells with increased infiltration of PD-L1+ TAMs as well as distant alterations in the bone marrow (BM). Our results demonstrate that glioblastomas exploit cell surface O-linked glycans for local and distant immune modulation.

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Tn Antigen, ≥99.0% (TLC)