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
{"title":"Protumoral lipid droplet–loaded macrophages are enriched in human glioblastoma and can be therapeutically targeted","authors":"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","doi":"10.1126/scitranslmed.adk1168","DOIUrl":null,"url":null,"abstract":"<div >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 <i>O</i>-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.</div>","PeriodicalId":21580,"journal":{"name":"Science Translational Medicine","volume":null,"pages":null},"PeriodicalIF":15.8000,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Science Translational Medicine","FirstCategoryId":"3","ListUrlMain":"https://www.science.org/doi/10.1126/scitranslmed.adk1168","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
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.
期刊介绍:
Science Translational Medicine is an online journal that focuses on publishing research at the intersection of science, engineering, and medicine. The goal of the journal is to promote human health by providing a platform for researchers from various disciplines to communicate their latest advancements in biomedical, translational, and clinical research.
The journal aims to address the slow translation of scientific knowledge into effective treatments and health measures. It publishes articles that fill the knowledge gaps between preclinical research and medical applications, with a focus on accelerating the translation of knowledge into new ways of preventing, diagnosing, and treating human diseases.
The scope of Science Translational Medicine includes various areas such as cardiovascular disease, immunology/vaccines, metabolism/diabetes/obesity, neuroscience/neurology/psychiatry, cancer, infectious diseases, policy, behavior, bioengineering, chemical genomics/drug discovery, imaging, applied physical sciences, medical nanotechnology, drug delivery, biomarkers, gene therapy/regenerative medicine, toxicology and pharmacokinetics, data mining, cell culture, animal and human studies, medical informatics, and other interdisciplinary approaches to medicine.
The target audience of the journal includes researchers and management in academia, government, and the biotechnology and pharmaceutical industries. It is also relevant to physician scientists, regulators, policy makers, investors, business developers, and funding agencies.