Astrocytic trans-differentiation completes a multicellular paracrine feedback loop required for medulloblastoma tumor growth
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE109750 | GEO | 2019/12/31
REPOSITORIES: GEO
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Project description:Glioblastomas are aggressive primary brain cancers that invariably recur as therapy-resistant tumors. Myeloid cells control glioblastoma malignancy, but their dynamics during disease progression remains poorly understood. By relying on single-cell RNA and protein profiling, we mapped the glioblastoma immune landscape in newly diagnosed and recurrent patients and in mouse tumors. This revealed a large and diverse myeloid compartment, with dendritic cell and macrophage populations that were conserved across species and were 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 (Mo-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 Mo-TAMs upon recurrence, especially in hypoxic tumor environments. Our results unravel the glioblastoma myeloid landscape and provide a framework for future therapeutic interventions.
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