Helmholtz Gemeinschaft


Glioma-derived galectin-1 regulates innate and adaptive antitumor immunity

Item Type:Article
Title:Glioma-derived galectin-1 regulates innate and adaptive antitumor immunity
Creators Name:Verschuere, T., Toelen, J., Maes, W., Poirier, F., Boon, L., Tousseyn, T., Mathivet, T., Gerhardt, H., Mathieu, V., Kiss, R., Lefranc, F., Van Gool, S.W. and De Vleeschouwer, S.
Abstract: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.
Keywords:Alectin-1, Glioblastoma, Tumor-Infiltrating Myeloid Cells, Dendritic Cell Immunotherapy, Angiogenesis, Animals, Mice
Source:International Journal of Cancer
Page Range:873-884
Date:15 February 2014
Official Publication:https://doi.org/10.1002/ijc.28426
PubMed:View item in PubMed

Repository Staff Only: item control page

Open Access
MDC Library