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Updated: Jun 15, 2025
In Vitro Phagocytosis of Myelin Debris by Bone Marrow-Derived Macrophages
Published on: December 30, 2017
Lipid-Laden Macrophages Recycle Myelin to Feed Glioblastoma
Lizhi Pang1, Fei Zhou1, Peiwen Chen1
1Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
Abstract:
Tumor-associated microglia and macrophages (TAM) make up the largest immune cell population in the glioblastoma (GBM) tumor microenvironment. Given the heterogeneity and plasticity of TAMs in the GBM tumor microenvironment, 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 glycoprotein nonmetastatic melanoma protein Bhigh lipid-laden microglia and macrophages (LLM) in GBM. Mesenchymal-like GBM cells help generate the LLM phenotype. Reciprocally, LLMs are epigenetically rewired to recycle myelin and transfer the lipid from myelin to cancer cells, fueling mesenchymal-like GBM progression in a liver X receptor/ABCA1-dependent manner. Together, leveraging LLMs opens new therapeutic possibilities for rewiring the metabolism-mediated tumor-TAM interaction during GBM progression.
Insights
Glioblastoma tumor cells and lipid-laden macrophages form a symbiotic relationship. This interaction fuels tumor growth, offering new therapeutic targets for glioblastoma (GBM) treatment.
Area of Science:
- Neuro-oncology
- Cancer immunology
- Tumor microenvironment
Background:
- Tumor-associated microglia and macrophages (TAM) are the most abundant immune cells in the glioblastoma (GBM) tumor microenvironment.
- Understanding the dynamic interplay between cancer cells and TAMs is critical for advancing GBM therapies.
Purpose of the Study:
- To identify and characterize novel TAM subpopulations within the GBM tumor microenvironment.
- To elucidate the functional and metabolic interactions between GBM cells and TAMs.
Main Methods:
- Identification of a distinct subpopulation of glycoprotein nonmetastatic melanoma protein B-high lipid-laden microglia and macrophages (LLM) in GBM.
- Analysis of the reciprocal relationship between mesenchymal-like GBM cells and LLMs.
Main Results:
- Mesenchymal-like GBM cells induce the LLM phenotype in TAMs.
- LLMs are epigenetically reprogrammed to internalize and transfer myelin-derived lipids to GBM cells.
- This lipid transfer fuels mesenchymal-like GBM progression via the liver X receptor/ABCA1 pathway.
Conclusions:
- Lipid-laden macrophages represent a key metabolic symbiont in GBM.
- Targeting the LLM phenotype and its metabolic functions presents a promising therapeutic strategy for GBM.
