Lipid-Laden Macrophages Recycle Myelin to Feed Glioblastoma

Tumor-associated microglia and macrophages (TAMs) make up the largest immune cell population in the glioblastoma (GBM) tumor microenvironment (TME). Given the heterogeneity and plasticity of TAMs in the GBM TME, understanding the context-dependent cancer cell-TAM symbiotic interaction is crucial for understanding GBM biology and developing effective therapies. In a recent issue of Cell, Kloosterman and colleagues identified a subpopulation of GPNMBhigh lipid-laden microglia and macrophages (LLMs) in GBM. Mesenchymal-like (MES-like) GBM cells help to generate the LLM phenotype. Reciprocally, LLMs are epigenetically rewired to recycle myelin and transfer the lipid from myelin to cancer cells, fueling MES-like GBM progression in an LXR/ABCA1-dependent manner. Together, leveraging LLMs opens new therapeutic possibilities for rewiring the metabolism-mediated tumor-TAM interaction during GBM progression.