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

Ana Rita Pombo Antunes, Isabelle Scheyltjens, Francesca Lodi, Julie Messiaen, Asier Antoranz, Johnny Duerinck, Daliya Kancheva, Liesbet Martens, Karen De Vlaminck, Hannah Van Hove, Signe Schmidt Kjølner Hansen, Francesca Maria Bosisio, Koen Van der Borght, Steven De Vleeschouwer, Raf Sciot, Luc Bouwens, Michiel Verfaillie, Niels Vandamme, Roosmarijn E Vandenbroucke, Olivier De WeverYvan Saeys, Martin Guilliams, Conny Gysemans, Bart Neyns, Frederik De Smet, Diether Lambrechts, Jo A Van Ginderachter, Kiavash Movahedi

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)595-610
Number of pages16
JournalNature Neuroscience
Volume24
Issue number4
DOIs
Publication statusPublished - Apr 2021

Keywords

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

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