作者
Valeria Governa,Kelin Gonçalves de Oliveira,Anna Bång-Rudenstam,Svenja Offer,Myriam Cerezo-Magaña,Jiaxin Li,Sarah Beyer,Maria C. Johansson,Ann‐Sofie Månsson,Charlotte Edvardsson,Faris Durmo,Emma Gustafsson,Axel Boukredine,Pauline Jeannot,Katja Schmidt,Emelie Gezelius,Julien A. Menard,Raquel Garza,Johan Jakobsson,Therese de Neergaard,Pia C. Sundgren,Aliisa M. Tiihonen,Hannu Haapasalo,Kirsi J. Rautajoki,Pontus Nordenfelt,Anna Darabi,Karin Forsberg‐Nilsson,Alexander Pietras,Hugo Talbot,Johan Bengzon,Mattias Belting
摘要
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.