Single-cell profiling of myeloid cells in glioblastoma across species and disease stage reveals macrophage competition and specialization.

Animals Brain Neoplasms / immunology Glioblastoma / immunology Humans Mice Single-Cell Analysis Tumor-Associated Macrophages / cytology

Journal

Nature neuroscience
ISSN: 1546-1726
Titre abrégé: Nat Neurosci
Pays: United States
ID NLM: 9809671

Informations de publication

Date de publication:
04 2021
Historique:
received: 27 03 2020
accepted: 22 12 2020
pubmed: 31 3 2021
medline: 24 4 2021
entrez: 30 3 2021
Statut: ppublish

Résumé

Glioblastomas are aggressive primary brain cancers that recur as therapy-resistant tumors. Myeloid cells control glioblastoma malignancy, but their dynamics during disease progression remain poorly understood. Here, we employed single-cell RNA sequencing and CITE-seq to map the glioblastoma immune landscape in mouse tumors and in patients with newly diagnosed disease or recurrence. This revealed a large and diverse myeloid compartment, with dendritic cell and macrophage populations that were conserved across species and dynamic across disease stages. Tumor-associated macrophages (TAMs) consisted of microglia- or monocyte-derived populations, with both exhibiting additional heterogeneity, including subsets with conserved lipid and hypoxic signatures. Microglia- and monocyte-derived TAMs were self-renewing populations that competed for space and could be depleted via CSF1R blockade. Microglia-derived TAMs were predominant in newly diagnosed tumors, but were outnumbered by monocyte-derived TAMs following recurrence, especially in hypoxic tumor environments. Our results unravel the glioblastoma myeloid landscape and provide a framework for future therapeutic interventions.

Identifiants

DOI: 10.1038/s41593-020-00789-y PMID: 33782623
pubmed: 33782623
doi: 10.1038/s41593-020-00789-y
pii: 10.1038/s41593-020-00789-y
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

595-610

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Auteurs

Ana Rita Pombo Antunes (AR)

Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Brussels, Belgium.
Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium.

Isabelle Scheyltjens (I)

Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Brussels, Belgium.
Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium.
ORCID: 0000-0002-2260-2921

Francesca Lodi (F)

Laboratory of Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium.
VIB-KU Leuven Center for Cancer Biology, VIB, Leuven, Belgium.

Julie Messiaen (J)

Laboratory for Precision Cancer Medicine, Translational Cell and Tissue Research Unit, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.

Asier Antoranz (A)

Laboratory for Precision Cancer Medicine, Translational Cell and Tissue Research Unit, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.

Johnny Duerinck (J)

Department of Neurosurgery, UZ Brussels, Brussels, Belgium.
ORCID: 0000-0001-9869-9806

Daliya Kancheva (D)

Janssen Pharmaceuticals, Beerse, Belgium.
ORCID: 0000-0001-6222-0461

Liesbet Martens (L)

Laboratory of Myeloid Cell Ontogeny and Functional Specialization, VIB Center for Inflammation Research, Ghent, Belgium.
Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
Laboratory of Myeloid Cell Heterogeneity and Function, VIB Center for Inflammation Research, Ghent, Belgium.
ORCID: 0000-0001-9180-7456

Karen De Vlaminck (K)

Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Brussels, Belgium.
Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium.
ORCID: 0000-0002-5595-1482

Hannah Van Hove (H)

Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Brussels, Belgium.
Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium.
ORCID: 0000-0002-0412-6474

Signe Schmidt Kjølner Hansen (SS)

Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Brussels, Belgium.
Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium.

Francesca Maria Bosisio (FM)

Translational Cell and Tissue Research Unit, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.

Koen Van der Borght (K)

Janssen Pharmaceuticals, Beerse, Belgium.

Steven De Vleeschouwer (S)

Department of Neurosurgery, UZ Leuven, Leuven, Belgium.
Laboratory for Experimental Neurosurgery and Neuroanatomy, Department of Neurosciences and Leuven Brain Institute (LBI), KU Leuven, Leuven, Belgium.
ORCID: 0000-0002-9576-9917

Raf Sciot (R)

Translational Cell and Tissue Research Unit, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
ORCID: 0000-0003-2244-5839

Luc Bouwens (L)

Cell Differentiation Lab, Vrije Universiteit Brussel, Brussels, Belgium.

Michiel Verfaillie (M)

Department of Neurosurgery, Europe Hospitals Saint Elisabeth, Ukkel, Belgium.

Niels Vandamme (N)

Data Mining and Modeling for Biomedicine, VIB Center for Inflammation Research, Ghent, Belgium.
Department of Applied Mathematics, Computer Science and Statistics, Ghent University, Ghent, Belgium.

Roosmarijn E Vandenbroucke (RE)

VIB Center for Inflammation Research, Gent, Belgium.
Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
ORCID: 0000-0002-8327-620X

Olivier De Wever (O)

Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium.
Laboratory for Experimental Cancer Research, Ghent University, Ghent, Belgium.

Yvan Saeys (Y)

Data Mining and Modeling for Biomedicine, VIB Center for Inflammation Research, Ghent, Belgium.
Department of Applied Mathematics, Computer Science and Statistics, Ghent University, Ghent, Belgium.

Martin Guilliams (M)

Laboratory of Myeloid Cell Ontogeny and Functional Specialization, VIB Center for Inflammation Research, Ghent, Belgium.
Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
ORCID: 0000-0003-3525-7570

Conny Gysemans (C)

Clinical and Experimental Endocrinology (CEE), KU Leuven, Leuven, Belgium.

Bart Neyns (B)

Department of Medical Oncology, UZ Brussels, Brussels, Belgium.

Frederik De Smet (F)

Laboratory for Precision Cancer Medicine, Translational Cell and Tissue Research Unit, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
ORCID: 0000-0002-6669-3335

Diether Lambrechts (D)

Laboratory of Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium.
VIB-KU Leuven Center for Cancer Biology, VIB, Leuven, Belgium.
ORCID: 0000-0002-3429-302X

Jo A Van Ginderachter (JA)

Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Brussels, Belgium.
Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium.

Kiavash Movahedi (K)

Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Brussels, Belgium. kiavash.movahedi@vub.be.
Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium. kiavash.movahedi@vub.be.
ORCID: 0000-0002-0826-4399

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Single-cell profiling of myeloid cells in...
questionsmedicales.fr › Maladies du système nerveux › Tumeurs du système nerveux › Tumeurs du système nerveux central › Tumeurs du cerveau › Single-cell profiling of myeloid cells in...
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Tumeurs du tissu nerveux › Tumeurs neuroectodermiques › Tumeurs neuroépitheliales › Gliome › Astrocytome › Glioblastome › Single-cell profiling of myeloid cells in...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Single-cell profiling of myeloid cells in...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Single-cell profiling of myeloid cells in...
questionsmedicales.fr › Techniques d'investigation › Techniques cytologiques › Analyse sur cellule unique › Single-cell profiling of myeloid cells in...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Phagocytes › Macrophages › Macrophages associés aux tumeurs › Single-cell profiling of myeloid cells in...