Protumoral lipid droplet-loaded macrophages are enriched in human glioblastoma and can be therapeutically targeted
(2024) In Science Translational Medicine 16(771). p.1168-1168- 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... (More)
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.
(Less)
- author
- organization
-
- Tumor microenvironment
- Tumor microenvironment (research group)
- LUCC: Lund University Cancer Centre
- Cancerepidemiology and radiation
- Research Group Lung Cancer (research group)
- Neurosurgery
- StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
- Diagnostic Radiology, (Lund)
- Human Neural Developmental Biology (research group)
- Division of Translational Cancer Research
- Brain Tumor Biology (research group)
- Molecular Neurogenetics (research group)
- MultiPark: Multidisciplinary research focused on Parkinson's disease
- Quantitative immunobiology (research group)
- Neuroradiology (research group)
- Infection Medicine (BMC)
- SEBRA Sepsis and Bacterial Resistance Alliance (research group)
- epIgG (research group)
- LTH Profile Area: Photon Science and Technology
- NanoLund: Centre for Nanoscience
- LTH Profile Area: Nanoscience and Semiconductor Technology
- Glioma immunotherapy group (research group)
- publishing date
- 2024-10-30
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Science Translational Medicine
- volume
- 16
- issue
- 771
- pages
- 1168 - 1168
- publisher
- American Association for the Advancement of Science (AAAS)
- external identifiers
-
- scopus:85208163780
- pmid:39475570
- ISSN
- 1946-6242
- DOI
- 10.1126/scitranslmed.adk1168
- language
- English
- LU publication?
- yes
- id
- 39ea3991-0e17-473f-bd1e-b8c859646a8a
- date added to LUP
- 2024-12-18 09:36:45
- date last changed
- 2025-07-31 17:24:47
@article{39ea3991-0e17-473f-bd1e-b8c859646a8a, abstract = {{<p>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.</p>}}, author = {{Governa, Valeria and de Oliveira, Kelin Gonçalves and Bång-Rudenstam, Anna and Offer, Svenja and Cerezo-Magaña, Myriam and Li, Jiaxin and Beyer, Sarah and Johansson, Maria C. and Månsson, Ann Sofie and Edvardsson, Charlotte and Durmo, Faris and Gustafsson, Emma and Boukredine, Axel and Jeannot, Pauline and Schmidt, Katja and Gezelius, Emelie and Menard, Julien A. and Garza, Raquel and Jakobsson, Johan and de Neergaard, Therese and Sundgren, Pia C. and Tiihonen, Aliisa M. and Haapasalo, Hannu and Rautajoki, Kirsi J. and Nordenfelt, Pontus and Darabi, Anna and Forsberg-Nilsson, Karin and Pietras, Alexander and Talbot, Hugo and Bengzon, Johan and Belting, Mattias}}, issn = {{1946-6242}}, language = {{eng}}, month = {{10}}, number = {{771}}, pages = {{1168--1168}}, publisher = {{American Association for the Advancement of Science (AAAS)}}, series = {{Science Translational Medicine}}, title = {{Protumoral lipid droplet-loaded macrophages are enriched in human glioblastoma and can be therapeutically targeted}}, url = {{http://dx.doi.org/10.1126/scitranslmed.adk1168}}, doi = {{10.1126/scitranslmed.adk1168}}, volume = {{16}}, year = {{2024}}, }