Protumoral lipid droplet-loaded macrophages are enriched in human glioblastoma and can be therapeutically targeted

Governa V, de Oliveira KG, Bång-Rudenstam A, Offer S, Cerezo-Magaña M, Li J, Beyer S, Johansson MC, Månsson AS, Edvardsson C, Durmo F, Gustafsson E, Boukredine A, Jeannot P, Schmidt K, Gezelius E, Menard JA, Garza R, Jakobsson J, de Neergaard T, Sundgren PC, Tiihonen AM, Haapasalo H, Rautajoki KJ, Nordenfelt P, Darabi A, Forsberg-Nilsson K, Pietras A, Talbot H, Bengzon J, Belting M (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Science Translational Medicine American Association for the Advancement of Science

Book Volume: 16

Pages Range: eadk1168-

Journal Issue: 771

DOI: 10.1126/scitranslmed.adk1168

Abstract

Glioblastoma presents a formidable clinical challenge because of its complex microenvironment. Here, we characterized tumor-associated foam cells (TAFs), a type of lipid droplet-loaded macrophage, in human glioblastoma. Through extensive analyses of patient tumors, together with in vitro and in vivo investigations, we found that TAFs exhibit distinct protumorigenic characteristics related to hypoxia, mesenchymal transition, angiogenesis, and impaired phagocytosis, and their presence correlates with worse outcomes for patients with glioma. We further demonstrated that TAF formation is facilitated by lipid scavenging from extracellular vesicles released by glioblastoma cells. We found that targeting key enzymes involved in lipid droplet formation, such as diacylglycerol O-acyltransferase or long-chain acyl-CoA synthetase, effectively disrupted TAF functionality. Together, these data highlight TAFs as a prominent immune cell population in glioblastoma and provide insights into their contribution to the tumor microenvironment. Disrupting lipid droplet formation to target TAFs may represent an avenue for future therapeutic development for glioblastoma.

Authors with CRIS profile

Katja Schmidt Department of Medicine 3 – Rheumatology and Immunology

Involved external institutions

Lund University / Lunds universitet SE Sweden (SE) Tampere University Hospital / Tampereen yliopistollinen sairaala (TAYS) FI Finland (FI) Uppsala University SE Sweden (SE) Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich DE Germany (DE)

How to cite

APA:

Governa, V., de Oliveira, K.G., Bång-Rudenstam, A., Offer, S., Cerezo-Magaña, M., Li, J.,... Belting, M. (2024). Protumoral lipid droplet-loaded macrophages are enriched in human glioblastoma and can be therapeutically targeted. Science Translational Medicine, 16(771), eadk1168-. https://doi.org/10.1126/scitranslmed.adk1168

MLA:

Governa, Valeria, et al. "Protumoral lipid droplet-loaded macrophages are enriched in human glioblastoma and can be therapeutically targeted." Science Translational Medicine 16.771 (2024): eadk1168-.

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