TY - JOUR
T1 - Protumoral lipid droplet-loaded macrophages are enriched in human glioblastoma and can be therapeutically targeted
AU - Governa, Valeria
AU - de Oliveira, Kelin Gonçalves
AU - Bång-Rudenstam, Anna
AU - Offer, Svenja
AU - Cerezo-Magaña, Myriam
AU - Li, Jiaxin
AU - Beyer, Sarah
AU - Johansson, Maria C.
AU - Månsson, Ann Sofie
AU - Edvardsson, Charlotte
AU - Durmo, Faris
AU - Gustafsson, Emma
AU - Boukredine, Axel
AU - Jeannot, Pauline
AU - Schmidt, Katja
AU - Gezelius, Emelie
AU - Menard, Julien A.
AU - Garza, Raquel
AU - Jakobsson, Johan
AU - de Neergaard, Therese
AU - Sundgren, Pia C.
AU - Tiihonen, Aliisa M.
AU - Haapasalo, Hannu
AU - Rautajoki, Kirsi J.
AU - Nordenfelt, Pontus
AU - Darabi, Anna
AU - Forsberg-Nilsson, Karin
AU - Pietras, Alexander
AU - Talbot, Hugo
AU - Bengzon, Johan
AU - Belting, Mattias
PY - 2024/10/30
Y1 - 2024/10/30
N2 - 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.
AB - 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.
U2 - 10.1126/scitranslmed.adk1168
DO - 10.1126/scitranslmed.adk1168
M3 - Article
C2 - 39475570
AN - SCOPUS:85208163780
SN - 1946-6242
VL - 16
SP - eadk1168
JO - Science Translational Medicine
JF - Science Translational Medicine
IS - 771
ER -