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Single-cell profiling and zebrafish avatars reveal LGALS1 as immunomodulating target in glioblastoma

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Item Type:Article
Title:Single-cell profiling and zebrafish avatars reveal LGALS1 as immunomodulating target in glioblastoma
Creators Name:Finotto, L. and Cole, B. and Giese, W. and Baumann, E. and Claeys, A. and Vanmechelen, M. and Decraene, B. and Derweduwe, M. and Dubroja Lakic, N. and Shankar, G. and Nagathihalli Kantharaju, M. and Albrecht, J.P. and Geudens, I. and Stanchi, F. and Ligon, K.L. and Boeckx, B. and Lambrechts, D. and Harrington, K. and Van Den Bosch, L. and De Vleeschouwer, S. and De Smet, F. and Gerhardt, H.
Abstract:Glioblastoma (GBM) remains the most malignant primary brain tumor, with a median survival rarely exceeding 2 years. Tumor heterogeneity and an immunosuppressive microenvironment are key factors contributing to the poor response rates of current therapeutic approaches. GBM-associated macrophages (GAMs) often exhibit immunosuppressive features that promote tumor progression. However, their dynamic interactions with GBM tumor cells remain poorly understood. Here, we used patient-derived GBM stem cell cultures and combined single-cell RNA sequencing of GAM-GBM co-cultures and real-time in vivo monitoring of GAM-GBM interactions in orthotopic zebrafish xenograft models to provide insight into the cellular, molecular, and spatial heterogeneity. Our analyses revealed substantial heterogeneity across GBM patients in GBM-induced GAM polarization and the ability to attract and activate GAMs—features that correlated with patient survival. Differential gene expression analysis, immunohistochemistry on original tumor samples, and knock-out experiments in zebrafish subsequently identified LGALS1 as a primary regulator of immunosuppression. Overall, our work highlights that GAM-GBM interactions can be studied in a clinically relevant way using co-cultures and avatar models, while offering new opportunities to identify promising immune-modulating targets.
Keywords:Glioblastoma, LGALS1, Macrophages, scRNA-seq, Zebrafish Avatars, Animals, Zebrafish
Source:EMBO Molecular Medicine
Publisher:EMBO Press / Wiley
Page Range:e18144
Date:8 November 2023
Official Publication:https://doi.org/10.15252/emmm.202318144
PubMed:View item in PubMed

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