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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\n            <jats:italic>O<\/jats:italic>\n            -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.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.adk1168","type":"journal-article","created":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T17:59:03Z","timestamp":1730311143000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":55,"title":["Protumoral lipid droplet\u2013loaded macrophages are enriched in human glioblastoma and can be therapeutically targeted"],"prefix":"10.1126","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9999-0590","authenticated-orcid":true,"given":"Valeria","family":"Governa","sequence":"first","affiliation":[{"name":"Division of Oncology, Department of Clinical Sciences, Lund, Lund University, Lund 221 00, 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