Macrophage-mediated myelin recycling fuels brain cancer malignancy![]()
Daan J Kloosterman,
Cell, 2024
In metabolically constrained settings, glioblastomas depended on the tumor microenvironment (TME) to fulfill their heightened energy requirements. Investigators, employing single-cell and multi-omics analyses, explored the heterogeneity of the TME and uncovered subsets of tumor-associated macrophages (TAMs) that had been metabolically reprogrammed and possessed protumorigenic characteristics. Notably, a subpopulation of TAMs, termed lipid-laden macrophages (LLMs), displayed immunosuppressive features and were particularly enriched in the invasive mesenchymal subtype of glioblastoma.These LLMs assumed the LLM phenotype by engulfing cholesterol-rich debris, and then, in an LXR/Abca1-dependent manner, they transferred lipids derived from this debris directly to cancer cells, further intensifying the metabolic demands of these cells. These discoveries offered profound insights into the interplay between immune and metabolic interactions during the progression of glioblastoma and established a foundation for uncovering vulnerabilities in the targeted metabolism of glioblastoma. This research not only deepened our comprehension of the immune-metabolic interplay associated with glioblastoma progression but also presented potential targets for devising innovative therapeutic strategies.DOI: 10.1016/j.cell.2024.07.030.
Glycolysis in hepatic stellate cells coordinates fibrogenic extracellular vesicle release spatially to amplify liver fibrosisSci Adv, 2024
Globally, around 2 million individuals perish annually from liver diseases and cirrhosis. In recent times, a significant number of researchers have been intensely investigating the role of cellular and molecular heterogeneity in the advancement of liver fibrosis towards cirrhosis. This heterogeneity encompasses a distinct subset of hepatic stellate cells (HSCs), which propel fibrosis through the substantial deposition of extracellular matrix in discrete liver regions. Through their project, the researchers established that glycolysis specific to HSCs enhances liver fibrosis in vivo by elevating extracellular vesicle (EV)-associated pathways surrounding the fibrotic core. More profound analysis revealed that the glycolytic signaling in HSCs facilitates the emission of fibrotic EVs in a spatially orchestrated fashion, thereby exacerbating liver fibrosis. Consequently, targeting glycolytic enzymes like HK2 and the ensuing epigenetic mechanisms could present a therapeutic target for liver fibrosis treatment.
DOI: 10.1126/sciadv.adn5228.
Editor & Reviewer: Congci Yu
