Title: Glioma-derived galectin-1 regulates innate and adaptive antitumor immunity
Authors: Verschuere, Tina ×
Toelen, Jaan
Maes, Wim
Poirier, Françoise
Boon, Louis
Tousseyn, Thomas
Mathivet, Thomas
Gerhardt, Holger
Mathieu, Veronique
Kiss, Robert
Lefranc, Florence
Van Gool, Stefaan
De Vleeschouwer, Steven #
Issue Date: Aug-2013
Publisher: Wiley-Liss
Series Title: International Journal of Cancer vol:134 issue:4 pages:873-884
Article number: 10.1002/ijc.28426
Abstract: Galectin-1 is a glycan-binding protein which is involved in the aggressive nature of glioblastoma (GBM) in part by stimulating angiogenesis. In different cancer models, galectin-1 has been demonstrated to play a pivotal role in tumor-mediated immune evasion especially by modulating cells of the adaptive immune system. It is yet unknown however whether the absence or presence of galectin-1 within the glioma microenvironment also causes qualitative or quantitative differences in innate and/or adaptive antitumor immune responses. All experiments were performed in the orthotopic GL261 mouse high-grade glioma model. Stable galectin-1 knockdown was achieved via transduction of parental GL261 tumor cells with a lentiviral vector encoding a galectin-1-targeting miRNA. We demonstrated that the absence of tumor-derived but not of host-derived galectin-1 significantly prolonged the survival of glioma-bearing mice as such and in combination with dendritic cell (DC)-based immunotherapy. Both flow cytometric and pathological analysis revealed that the silencing of glioma-derived galectin-1 significantly decreased the amount of brain-infiltrating macrophages and myeloid-derived suppressor cells (MDSC) in tumor-bearing mice. Additionally, we revealed a pro-angiogenic role for galectin-1 within the glioma microenvironment. The data provided in this study reveal a pivotal role for glioma-derived galectin-1 in the regulation of myeloid cell accumulation within the glioma microenvironment, the most abundant immune cell population in high-grade gliomas. Furthermore, the prolonged survival observed in untreated and DC-vaccinated glioma-bearing mice upon the silencing of tumor-derived galectin-1 strongly suggest that the in vivo targeting of tumor-derived galectin-1 might offer a promising and realistic adjuvant treatment modality in patients diagnosed with GBM. © 2013 Wiley Periodicals, Inc.
ISSN: 0020-7136
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Pediatric Immunology
Organ Systems (+)
Translational Cell & Tissue Research
Vascular Patterning Laboratory (Vesalius Research Center) (+)
Research Group Experimental Neurosurgery and Neuroanatomy
× corresponding author
# (joint) last author

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