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.

中文翻译：

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载有前瘤状脂滴的巨噬细胞在人胶质母细胞瘤中富集，可以作为治疗靶向


胶质母细胞瘤由于其复杂的微环境而提出了艰巨的临床挑战。在这里，我们在人胶质母细胞瘤中表征了肿瘤相关泡沫细胞 （TAF），这是一种载有脂滴的巨噬细胞。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、间充质转化、血管生成和吞噬作用受损相关的独特促肿瘤特性，并且它们的存在与神经胶质瘤患者的不良预后相关。我们进一步证明，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，如甘油二酯 O -酰基转移酶或长链酰基辅酶 A 合成酶，有效地破坏了 TAF 功能。总之，这些数据突出了 TAF 是胶质母细胞瘤中一种重要的免疫细胞群，并提供了对它们对肿瘤微环境贡献的见解。破坏脂滴形成以靶向 TAFs 可能代表了胶质母细胞瘤未来治疗开发的途径。