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

Tijdschriftbijdrage - Tijdschriftartikel

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.

Tijdschrift: Nature Neuroscience
ISSN: 1097-6256
Issue: 4
Volume: 24
Pagina's: 595-610
Aantal pagina's: 16
Jaar van publicatie:2021
Trefwoorden:Animals, Brain Neoplasms/immunology, Glioblastoma/immunology, Humans, Mice, Single-Cell Analysis, Tumor-Associated Macrophages/cytology, Neurowetenschappen en Psychofarmacologie
  • Institutional Repository URL: https://cris.vub.be/ws/files/84167961/66692855.pdf
  • ORCID: /0000-0002-4401-4530/work/95764873
  • ORCID: /0000-0002-2260-2921/work/95764900
  • ORCID: /0000-0002-6484-5593/work/95764567
  • ORCID: /0000-0002-0826-4399/work/95764523
  • ORCID: /0000-0002-4442-7474/work/95764277
  • ORCID: /0000-0001-5767-7002/work/95764257
  • ORCID: /0000-0003-0658-5903/work/95762827
  • Scopus Id: 85103415654
  • DOI: https://doi.org/10.1038/s41593-020-00789-y
  • PubMed Id: 33782623