Projects per year
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 language | English |
---|---|
Pages (from-to) | 595-610 |
Number of pages | 16 |
Journal | Nature Neuroscience |
Volume | 24 |
Issue number | 4 |
DOIs | |
Publication status | Published - Apr 2021 |
Keywords
- Animals
- Brain Neoplasms/immunology
- Glioblastoma/immunology
- Humans
- Mice
- Single-Cell Analysis
- Tumor-Associated Macrophages/cytology
Fingerprint
Dive into the research topics of 'Single-cell profiling of myeloid cells in glioblastoma across species and disease stage reveals macrophage competition and specialization'. Together they form a unique fingerprint.Projects
- 1 Finished
-
SRP47: Strategic Research Programme: Molecular Imaging and targeting of macrophages in Inflammation (ITARMI)
Lahoutte, T., Van Ginderachter, J. & Devoogdt, N.
1/11/17 → 31/10/22
Project: Fundamental