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The immune microenvironment in ascites remains understudied, leaving the mechanism of ascites\u2010mediated abdominal metastasis obscure. Here, a single\u2010cell transcriptomic landscape of CD45\n                    <jats:sup>+<\/jats:sup>\n                    immune cells across multiple anatomical sites is depicted, including primary tumors, metastatic lesions, and ascites, from patients diagnosed with high\u2010grade serous ovarian carcinoma (HGSOC). A novel subset of perilipin 2 high (PLIN2\n                    <jats:sup>hi<\/jats:sup>\n                    ) macrophages are identified that are enriched in ascites and positively correlated with OC progression, hence being designated as \u201cascites\u2010associated macrophages (AAMs)\u201d. AAMs are lipid\u2010loaded with overexpression of the lipid droplet protein PLIN2. Overexpression or suppression of PLIN2 can enhance or inhibit tumor cell migration, invasion, and vascular permeability in vitro, which is also confirmed in vivo. Mechanistically, it is demonstrated that PLIN2 boosts HIF1\u03b1\/SPP1 signaling in macrophages, thereby exerting pro\u2010tumor functions. Finally, a PLIN2\u2010targeting liposome is designed to efficiently suppress ascites production and tumor metastasis. Taken together, this work provides a comprehensive characterization of the cancer\u2010promoting function and lipid\u2010rich property of ascites\u2010enriched PLIN2\n                    <jats:sup>hi<\/jats:sup>\n                    macrophages, establishes a link between lipid metabolism and hypoxia within the context of the ascites microenvironment, and elucidates the pivotal role of ascites in trans\u2010coelomic metastasis of OC.\n                  <\/jats:p>","DOI":"10.1002\/advs.202411314","type":"journal-article","created":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T22:25:08Z","timestamp":1739226308000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["PLIN2 Promotes Lipid Accumulation in Ascites\u2010Associated Macrophages and Ovarian Cancer Progression by HIF1\u03b1\/SPP1 Signaling"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2527-0237","authenticated-orcid":false,"given":"Hui","family":"Luo","sequence":"first","affiliation":[{"name":"Guangdong Provincial Engineering Research Center of Molecular Imaging Guangdong\u2010Hong Kong\u2010Macao University Joint Laboratory of Interventional Medicine The Fifth Affiliated Hospital of Sun Yat\u2010sen University  Zhuhai Guangdong 519000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolu","family":"She","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Engineering Research Center of Molecular Imaging Guangdong\u2010Hong Kong\u2010Macao University Joint Laboratory of Interventional Medicine The Fifth Affiliated Hospital of Sun Yat\u2010sen University  Zhuhai Guangdong 519000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yubo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guangdong 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