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Here, we analyzed cytotoxic lymphocytes [natural killer (NK), T, and innate T cells] from patients with HGSOC and observed widespread dysfunction across primary and metastatic sites. Although nutrient rich, ascites was immunosuppressive for all lymphocyte subsets. NK cell dysfunction was driven by uptake of polar lipids, with associated dysregulation in lipid storage. Phosphatidylcholine was a key immunosuppressive metabolite, disrupting NK cell membrane order and cytotoxicity. Blocking lipid uptake through SR-B1 protected NK cell antitumor functions in ascites. These findings offer insights into immune suppression in HGSOC and have important implications for the design of future immunotherapies.<\/jats:p>","DOI":"10.1126\/sciimmunol.adr4795","type":"journal-article","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T13:58:16Z","timestamp":1746799096000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":43,"title":["Uptake of lipids from ascites drives NK cell metabolic dysfunction in ovarian cancer"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9001-8866","authenticated-orcid":true,"given":"Karen","family":"Slattery","sequence":"first","affiliation":[{"name":"School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3922-1874","authenticated-orcid":true,"given":"Cong-Hui","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eimear","family":"Mylod","sequence":"additional","affiliation":[{"name":"School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9559-4731","authenticated-orcid":true,"given":"John","family":"Scanlan","sequence":"additional","affiliation":[{"name":"School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8841-3525","authenticated-orcid":true,"given":"Barry","family":"Scott","sequence":"additional","affiliation":[{"name":"School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph Patrick","family":"Crowley","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orla","family":"McGowan","sequence":"additional","affiliation":[{"name":"School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin","family":"McManus","sequence":"additional","affiliation":[{"name":"School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Brennan","sequence":"additional","affiliation":[{"name":"School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland."},{"name":"Brigham &amp; 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