Glioma-derived galectin-1 regulates innate and adaptive antitumor immunity.
Galectin-1 is a glycan-binding protein, which is involved in the aggressiveness of glioblastoma (GBM) in part by stimulating angiogenesis. In different cancer models, galectin-1 has also 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 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.
Department of Neurosciences, Laboratory of Experimental Neurosurgery and Neuroanatomy, KU Leuven, Leuven, Belgium.
Tina
T
Verschuere
Jaan
J
Toelen
Wim
W
Maes
Françoise
F
Poirier
Louis
L
Boon
Thomas
T
Tousseyn
Thomas
T
Mathivet
Holger
H
Gerhardt
Veronique
V
Mathieu
Robert
R
Kiss
Florence
F
Lefranc
Stefaan W
SW
Van Gool
Steven
S
De Vleeschouwer
D056704:Adaptive Immunity / Q000276:immunology*; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D037483:Galectin 1 / Q000502:physiology*; D005910:Glioma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007113:Immunity, Innate / Q000276:immunology*; D007124:Immunoenzyme Techniques; D007167:Immunotherapy; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D037483:Galectin 1; D012333:RNA, Messenger
angiogenesis; dendritic cell immunotherapy; galectin-1; glioblastoma; tumor-infiltrating myeloid cells