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

Proc Natl Acad Sci U S A. 2020 Feb 18;117(7):3693-3703. doi: 10.1073/pnas.1907921117. Epub 2020 Feb 4.


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.

Keywords: O-linked glycosylation; glioblastoma; immunosuppression; macrophage galactose lectin; macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • Antigens, Differentiation, Myelomonocytic / genetics
  • Antigens, Differentiation, Myelomonocytic / immunology
  • Asialoglycoproteins / chemistry
  • Asialoglycoproteins / genetics
  • Asialoglycoproteins / immunology*
  • Glioblastoma / genetics
  • Glioblastoma / immunology*
  • Humans
  • Lectins, C-Type / chemistry
  • Lectins, C-Type / genetics
  • Lectins, C-Type / immunology*
  • Macrophages / immunology
  • Male
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Microglia / immunology
  • Polysaccharides / chemistry
  • Polysaccharides / immunology
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / immunology


  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Asialoglycoproteins
  • CD163 antigen
  • Clec10a protein, mouse
  • Lectins, C-Type
  • Membrane Proteins
  • Polysaccharides
  • Receptors, Cell Surface