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

IF 15.8 1区 医学 Q1 CELL BIOLOGY Science Translational Medicine Pub Date : 2024-10-30 DOI:10.1126/scitranslmed.adk1168
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
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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.
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人胶质母细胞瘤中富含原生质脂滴巨噬细胞,可以作为治疗靶点。
胶质母细胞瘤因其复杂的微环境而成为一项艰巨的临床挑战。在这里,我们描述了人类胶质母细胞瘤中肿瘤相关泡沫细胞(TAFs)的特征,TAFs是一种带有脂滴的巨噬细胞。通过对患者肿瘤的广泛分析以及体外和体内研究,我们发现TAFs表现出与缺氧、间质转化、血管生成和吞噬功能受损相关的明显原发肿瘤特征,而且它们的存在与胶质瘤患者的预后恶化相关。我们进一步证实,胶质母细胞瘤细胞释放的细胞外囊泡中的脂质清除促进了 TAF 的形成。我们发现,靶向参与脂滴形成的关键酶,如二酰甘油O-酰基转移酶或长链酰-CoA合成酶,可有效破坏TAF的功能。总之,这些数据凸显了TAFs是胶质母细胞瘤中一个重要的免疫细胞群,并为了解它们对肿瘤微环境的贡献提供了见解。破坏脂滴形成以靶向 TAFs 可能是未来开发胶质母细胞瘤疗法的一个途径。
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来源期刊
Science Translational Medicine
Science Translational Medicine CELL BIOLOGY-MEDICINE, RESEARCH & EXPERIMENTAL
CiteScore
26.70
自引率
1.20%
发文量
309
审稿时长
1.7 months
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.
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