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

Autor: Finotto L; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.; VIB - KU Leuven Center for Cancer Biology, VIB - KU Leuven, Leuven, Belgium.; The Laboratory for Precision Cancer Medicine, Translational Cell and Tissue Research Unit, Department of Imaging & Pathology, KU Leuven, Leuven, Belgium.; KU Leuven Institute for Single Cell Omics (LISCO), KU Leuven, Leuven, Belgium., Cole B; The Laboratory for Precision Cancer Medicine, Translational Cell and Tissue Research Unit, Department of Imaging & Pathology, KU Leuven, Leuven, Belgium.; KU Leuven Institute for Single Cell Omics (LISCO), KU Leuven, Leuven, Belgium., Giese W; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.; DZHK (German Center for Cardiovascular Research), Partner Site Berlin, Berlin, Germany., Baumann E; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.; Charité - Universitätsmedizin Berlin, Berlin, Germany., Claeys A; The Laboratory for Precision Cancer Medicine, Translational Cell and Tissue Research Unit, Department of Imaging & Pathology, KU Leuven, Leuven, Belgium.; KU Leuven Institute for Single Cell Omics (LISCO), KU Leuven, Leuven, Belgium., Vanmechelen M; The Laboratory for Precision Cancer Medicine, Translational Cell and Tissue Research Unit, Department of Imaging & Pathology, KU Leuven, Leuven, Belgium.; KU Leuven Institute for Single Cell Omics (LISCO), KU Leuven, Leuven, Belgium.; Department of Medical Oncology, University Hospitals Leuven, Leuven, Belgium., Decraene B; The Laboratory for Precision Cancer Medicine, Translational Cell and Tissue Research Unit, Department of Imaging & Pathology, KU Leuven, Leuven, Belgium.; KU Leuven Institute for Single Cell Omics (LISCO), KU Leuven, Leuven, Belgium.; Laboratory of Experimental Neurosurgery and Neuroanatomy, Department of Neurosciences, KU Leuven & Leuven Brain Institute (LBI), KU Leuven, Leuven, Belgium.; Department of Neurosurgery, University Hospitals Leuven, Leuven, Belgium., Derweduwe M; The Laboratory for Precision Cancer Medicine, Translational Cell and Tissue Research Unit, Department of Imaging & Pathology, KU Leuven, Leuven, Belgium.; KU Leuven Institute for Single Cell Omics (LISCO), KU Leuven, Leuven, Belgium., Dubroja Lakic N; The Laboratory for Precision Cancer Medicine, Translational Cell and Tissue Research Unit, Department of Imaging & Pathology, KU Leuven, Leuven, Belgium.; KU Leuven Institute for Single Cell Omics (LISCO), KU Leuven, Leuven, Belgium., Shankar G; The Laboratory for Precision Cancer Medicine, Translational Cell and Tissue Research Unit, Department of Imaging & Pathology, KU Leuven, Leuven, Belgium.; KU Leuven Institute for Single Cell Omics (LISCO), KU Leuven, Leuven, Belgium., Nagathihalli Kantharaju M; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.; Humboldt University of Berlin, Berlin, Germany., Albrecht JP; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.; Humboldt University of Berlin, Berlin, Germany., Geudens I; VIB - KU Leuven Center for Cancer Biology, VIB - KU Leuven, Leuven, Belgium., Stanchi F; VIB - KU Leuven Center for Cancer Biology, VIB - KU Leuven, Leuven, Belgium., Ligon KL; Center for Neuro-oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.; Department of Pathology, Harvard Medical School, Boston, MA, USA., Boeckx B; VIB - KU Leuven Center for Cancer Biology, VIB - KU Leuven, Leuven, Belgium.; KU Leuven Institute for Single Cell Omics (LISCO), KU Leuven, Leuven, Belgium.; Laboratory of Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium., Lambrechts D; VIB - KU Leuven Center for Cancer Biology, VIB - KU Leuven, Leuven, Belgium.; KU Leuven Institute for Single Cell Omics (LISCO), KU Leuven, Leuven, Belgium.; Laboratory of Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium., Harrington K; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.; Chan Zuckerberg Initiative, Redwood City, CA, USA., Van Den Bosch L; Laboratory of Neurobiology, Department of Neurosciences, Experimental Neurology & Leuven Brain Institute (LBI), KU Leuven, Leuven, Belgium.; VIB - KU Leuven Center for Brain & Disease Research, Laboratory of Neurobiology, VIB - KU Leuven, Leuven, Belgium., De Vleeschouwer S; KU Leuven Institute for Single Cell Omics (LISCO), KU Leuven, Leuven, Belgium.; Laboratory of Experimental Neurosurgery and Neuroanatomy, Department of Neurosciences, KU Leuven & Leuven Brain Institute (LBI), KU Leuven, Leuven, Belgium.; Department of Neurosurgery, University Hospitals Leuven, Leuven, Belgium., De Smet F; The Laboratory for Precision Cancer Medicine, Translational Cell and Tissue Research Unit, Department of Imaging & Pathology, KU Leuven, Leuven, Belgium.; KU Leuven Institute for Single Cell Omics (LISCO), KU Leuven, Leuven, Belgium., Gerhardt H; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.; DZHK (German Center for Cardiovascular Research), Partner Site Berlin, Berlin, Germany.; Charité - Universitätsmedizin Berlin, Berlin, Germany.; Berlin Institute of Health, Berlin, Germany.
Jazyk: angličtina
Zdroj: EMBO molecular medicine [EMBO Mol Med] 2023 Nov 08; Vol. 15 (11), pp. e18144. Date of Electronic Publication: 2023 Oct 04.
DOI: 10.15252/emmm.202318144
Abstrakt: 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.
(© 2023 The Authors. Published under the terms of the CC BY 4.0 license.)
Databáze: MEDLINE
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