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

Governa, Valeria LU ; de Oliveira, Kelin Gonçalves LU ; Bång-Rudenstam, Anna LU orcid ; Offer, Svenja LU ; Cerezo-Magaña, Myriam LU orcid ; Li, Jiaxin LU ; Beyer, Sarah LU ; Johansson, Maria C. LU ; Månsson, Ann Sofie LU and Edvardsson, Charlotte LU , et al. (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.

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organization
publishing date
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
  • pmid:39475570
  • scopus:85208163780
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
2025-08-14 05:11:00
@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}},
}