Description

The contribution of carbohydrate-dependent interactions in glioblastoma immune escape: New targets for check-point inhibition?

Sophie A. Dusoswa¹*, Valerie Wouters¹, Ernesto Rodriguez Camejo¹ Sandra van Vliet¹, Elga de Vries¹, David P. Noske², Thomas Würdinger^2,3, Yvette van Kooyk¹, Juan J. Garcia-Vallejo^{1 1}Department of Molecular Biology and Immunology, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands;
²Department of Neurosurgery, VU University Medical Center, Cancer Center Amsterdam, Amsterdam,The Netherlands; ³Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, USA
*Corresponding author

Glioblastoma (GBM) is the most aggressive form of brain cancer in which tumor associated macrophages and microglia account for up to 30% of the tumor mass. Macrophage galactose lectin (MGL) is a carbohydrate-specific receptor that is expressed by myeloid cells. MGL contributes to immune suppression by mediating IL-10 secretion and inducing apoptosis of effector T cells through direct interaction with CD45. MGL-ligands include truncated O-linked glycans, which have long been associated with metastasis formation and poor survival in breast- and colorectal cancer. Here we aim to elucidate the role of the MGL−MGL-ligand interaction in GBM immune escape. To this end, GBM, low-grade glioma (LGG) and epilepsy surgical samples were collected after approved informed consent. Expression of MGL and its ligands was investigated by flow cytometry, immunofluorescence microscopy, ELISA, and western blot. We detected significantly higher levels of MGL-ligand expression in GBM samples as compared to LGG and epilepsy samples. These MGL-ligands are expressed mainly in the perivascular space where we also find MGL⁺ perivascular macrophages. Moreover, we observed an association with increased progression free survival in patients with low expression of MGL ligands. These results suggest that GBM overexpress truncated O-linked glycans, associated with metastasis and poor survival. MGL-MGL-ligand interactions form a possible new immune checkpoint contributing to GBM immune escape and poor prognosis.