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

  • Antunes, Ana Rita Pombo;
  • Scheyltjens, Isabelle;
  • Lodi, Francesca;
  • Messiaen, Julie; 87491;
  • Antoranz, Asier;
  • Duerinck, Johnny;
  • Kancheva, Daliya;
  • Martens, Liesbet;
  • De Vlaminck, Karen;
  • Van Hove, Hannah;
  • Hansen, Signe Schmidt Kjolner;
  • Bosisio, Francesca Maria; 102815;
  • Van der Borght, Koen;
  • De Vleeschouwer, Steven; 39329;
  • Sciot, Raf; 10292;
  • Bouwens, Luc;
  • Verfaillie, Michiel;
  • Vandamme, Niels;
  • Vandenbroucke, Roosmarijn E;
  • De Wever, Olivier;
  • And 8 more
Publication Date
Mar 29, 2021
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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. / status: published

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