{
    "abstract": "The combination of immune checkpoint blockade and chemotherapies is the standard of care for triple-negative breast cancer (TNBC). However, initially, responsive tumors can still develop recurrences, suggesting acquired resistance mechanisms that remain poorly understood. Herein, we discover that TNBC cells surviving anti-programmed cell death protein-1 (anti-PD-1) and chemotherapy treatment accumulate neutral lipids. Disrupting lipid droplet formation in cancer cells reverses resistance and mitigates the immunosuppressive microenvironment. Single-cell RNA sequencing reveals a subset of neutrophils exhibiting a lipid-laden phenotype similar to adjacent tumor cells. Mechanistically, tumor-derived extracellular vesicles carrying lipids, including arachidonic acid (AA), mediate neutrophil reprogramming. Blocking dietary intake of omega-6 fatty acids or inhibiting fatty acid elongation for AA synthesis restores anti-tumor immunity and re-sensitizes the resistant tumors to anti-PD-1 and chemotherapy treatment. In human patients, AA metabolism-related pathways correlates with neutrophil enrichment. Overall, we demonstrate how lipid accumulation in TNBC cells leads to immune suppression and therapy resistance.",
    "authors": [
        {
            "affiliation": "Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.",
            "firstname": "Liqun",
            "initials": "L",
            "lastname": "Yu"
        },
        {
            "affiliation": "Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA.",
            "firstname": "Keziah",
            "initials": "K",
            "lastname": "Liebenberg"
        },
        {
            "affiliation": "Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Graduate Program in Integrative Molecular and Biomedical Sciences, Baylor College of Medicine, Houston, TX 77030, USA.",
            "firstname": "Yichao",
            "initials": "Y",
            "lastname": "Shen"
        },
        {
            "affiliation": "Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Graduate Program in Cancer and Cell Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.",
            "firstname": "Fengshuo",
            "initials": "F",
            "lastname": "Liu"
        },
        {
            "affiliation": "Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.",
            "firstname": "Zhan",
            "initials": "Z",
            "lastname": "Xu"
        },
        {
            "affiliation": "Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.",
            "firstname": "Xiaoxin",
            "initials": "X",
            "lastname": "Hao"
        },
        {
            "affiliation": "Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.",
            "firstname": "Ling",
            "initials": "L",
            "lastname": "Wu"
        },
        {
            "affiliation": "Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.",
            "firstname": "Weijie",
            "initials": "W",
            "lastname": "Zhang"
        },
        {
            "affiliation": "Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Medical Scientist Training Program, Baylor College of Medicine, Houston, TX 77030, USA.",
            "firstname": "Hilda L",
            "initials": "HL",
            "lastname": "Chan"
        },
        {
            "affiliation": "Metabolomics Core Facility, Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.",
            "firstname": "Bo",
            "initials": "B",
            "lastname": "Wei"
        },
        {
            "affiliation": "Metabolomics Core Facility, Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.",
            "firstname": "Philip L",
            "initials": "PL",
            "lastname": "Lorenzi"
        },
        {
            "affiliation": "Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.",
            "firstname": "Yang",
            "initials": "Y",
            "lastname": "Gao"
        },
        {
            "affiliation": "Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.",
            "firstname": "Igor",
            "initials": "I",
            "lastname": "Bado"
        },
        {
            "affiliation": "Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Graduate Program in Immunology and Microbiology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.",
            "firstname": "Luis",
            "initials": "L",
            "lastname": "Becerra-Dominguez"
        },
        {
            "affiliation": "Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Graduate Program in Cancer and Cell Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.",
            "firstname": "Charlotte Helena",
            "initials": "CH",
            "lastname": "Rivas"
        },
        {
            "affiliation": "Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Graduate Program in Integrative Molecular and Biomedical Sciences, Baylor College of Medicine, Houston, TX 77030, USA.",
            "firstname": "Sergio",
            "initials": "S",
            "lastname": "Aguirre"
        },
        {
            "affiliation": "Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Graduate Program in Immunology and Microbiology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.",
            "firstname": "Bradley C",
            "initials": "BC",
            "lastname": "Pingel"
        },
        {
            "affiliation": "Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Graduate Program in Cancer and Cell Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.",
            "firstname": "Yi-Hsuan",
            "initials": "YH",
            "lastname": "Wu"
        },
        {
            "affiliation": "Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.",
            "firstname": "Yunfeng",
            "initials": "Y",
            "lastname": "Ding"
        },
        {
            "affiliation": "Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.",
            "firstname": "Jun",
            "initials": "J",
            "lastname": "Liu"
        },
        {
            "affiliation": "Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.",
            "firstname": "David G",
            "initials": "DG",
            "lastname": "Edwards"
        },
        {
            "affiliation": "Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA.",
            "firstname": "Livia S",
            "initials": "LS",
            "lastname": "Eberlin"
        },
        {
            "affiliation": "Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA; McNair Medical Institute, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. Electronic address: xiangz@bcm.edu.",
            "firstname": "Xiang H-F",
            "initials": "XH",
            "lastname": "Zhang"
        }
    ],
    "conclusions": null,
    "copyrights": "Copyright \u00a9 2025 Elsevier Inc. All rights reserved.",
    "doi": "10.1016/j.immuni.2025.03.002",
    "journal": "Immunity",
    "keywords": [
        "arachidonic acid",
        "extracellular vesicles",
        "immunotherapy",
        "neutrophils",
        "triple negative breast cancer"
    ],
    "methods": null,
    "publication_date": "2025-03-30",
    "pubmed_id": "40157359\n32101663\n32053137\n29490946\n21907922\n33964209\n27374224\n25384214\n29949776\n37001504\n21948231\n19380772\n24784231\n23410636\n20081861\n16891410\n18268320\n30728496\n26668367\n33720040\n36827980\n37037615\n26759232\n30262472\n33450198\n31451770\n30523332\n24040298\n28754637\n37146584\n37002229\n32966785\n30787437\n28825705\n24658644\n29961579\n35549310\n26967288\n33312344\n22522925\n32711004\n25947066\n27791122\n29569717\n31932720\n29249690\n30742067\n30819964\n34799702\n30996346\n32958928\n33691090\n31160735\n32983128\n32694624\n26619320\n27999744\n19732719\n28753886\n30846479\n28346372\n32168452\n31178118\n37067911\n36780187\n36472914",
    "results": null,
    "title": "Tumor-derived arachidonic acid reprograms neutrophils to promote immune suppression and therapy resistance in triple-negative breast cancer.",
    "xml": "<Element 'PubmedArticle' at 0x788504f8aca0>"
}