ArticleImmunity2025
Tumor-derived arachidonic acid reprograms neutrophils to promote immune suppression and therapy resistance in triple-negative breast cancer.
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Article in Immunity, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 2 of them syntheses that pooled it.
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67citing papers in PubMed, 2 pooled it
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Who cites it
67 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- [Liquid Biopsy Revolutionizes the Precise Management of Tumors Across the Entire Course: Current Situation and Future Prospects].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2026Pooled it
- Metabolomics and metabolites in cancer diagnosis and treatment.Molecular biomedicine · 2025Pooled it
- NADPharmaceutical science advances · 2026Article
- Spatiotemporal dynamics of the host-tumor metabolic interface: Implications for precision nutritional oncology.Genes & diseases · 2026Review
- IGF2BP2 remodels the lung metastatic immune microenvironment to promote bladder cancer metastasis.Cellular & molecular immunology · 2026Article
- Ferroptosis and tumor microenvironment: orchestrating therapy resistance, immune evasion, and metastatic events.Medical oncology (Northwood, London, England) · 2026Review
- Photocontrolled nanosystem potentiates photo-chemoimmunotherapy against TNBC by integrating apoptosis/ferroptosis/ pyroptosis and STING activation.Materials today. Bio · 2026Article
- Targeting the tumor microenvironment: a new strategy for natural products in breast cancer therapy.Natural products and bioprospecting · 2026Review
- Leveraging Microphysiological Systems to Facilitate Neutrophil-Based Cancer Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Epigenetic Plasticity in Triple-Negative Breast Cancer: Mechanisms of Therapy Resistance, Biomarkers, and Therapeutic Vulnerabilities.Biomedicines · 2026Review
- Association of ALOX12-Mediated AA/12-HETE Metabolic Dysregulation with Abdominal Aortic Aneurysm Enlargement and Dissection.Journal of cardiovascular development and disease · 2026Article
- Lipid-Soluble Signaling Molecular Model Predicts Prognosis and Immunotherapy Response in Gastric Cancer.Lipids · 2026Article
- The Cancer Cell Metabolic Reprogramming Remodels the Tumor Microenvironment: Molecular Mechanisms and Therapeutic Strategies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Lipid droplet profiling during neutrophil differentiation by stimulated Raman scattering microscopy.Biotechnology progress · 2026Article
- ICAM1high Neutrophils Sculpt Tumor Evolution and Metastasis Through Symbiotic Adhesion and Reverse Migration.Cancer research · 2026Article
- Biophysical reprogramming of immunosuppressive neutrophils by cold atmospheric plasma reinvigorates antitumor immunity.Science advances · 2026Article
- Neutrophil-based immunotherapy: A metabolic lens on mechanisms and therapeutic implications.Clinical and translational medicine · 2026Review
- Tumor-derived stearic acid induces macrophage Egr2 signaling to suppress anti-tumor immunity in breast cancer.bioRxiv : the preprint server for biology · 2026Article
- Disruption of macrophage migration inhibitory factor signaling induces major tumor-associated macrophage phenotypes in human M2 macrophages.Molecular biomedicine · 2026Article
- Spatial organization of the TNBC tumor microenvironment: multicellular niches, T-cell bottlenecks, and therapeutic opportunities.Journal of translational medicine · 2026Review
7 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
23 authors.
Liqun YuLester 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.
Keziah LiebenbergDepartment of Surgery, Baylor College of Medicine, Houston, TX 77030, USA.
Yichao ShenLester 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.
Fengshuo LiuLester 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.
Zhan XuLester 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.
Xiaoxin HaoLester 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.
Ling WuLester 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.
Weijie ZhangLester 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.
Hilda L ChanLester 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.
Bo WeiMetabolomics Core Facility, Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Philip L LorenziMetabolomics Core Facility, Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Yang GaoLester 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.
Igor BadoLester 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.
Luis Becerra-DominguezLester 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.
Charlotte Helena RivasLester 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.
Sergio AguirreLester 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.
Bradley C PingelLester 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.
Yi-Hsuan WuLester 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.
Yunfeng DingLester 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.
Jun LiuLester 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.
David G EdwardsLester 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.
Livia S EberlinDan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA.
Xiang H-F ZhangLester 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.
Funding
Tumor BiologyP30CA125123 · NCI · BAYLOR COLLEGE OF MEDICINE · PI Michael M Ittmann · 2007 to 2026
$73.9MTranslational Research in Breast Cancer (SPORE)P50CA186784 · NCI · BAYLOR COLLEGE OF MEDICINE · PI MATTHEW J ELLIS · 2014 to 2026
$24.5MVISION RESEARCH CENTERP30EY002520 · NEI · BAYLOR COLLEGE OF MEDICINE · PI Samuel M Wu · 1985 to 2026
$14.8MOsteoclast-Independent Mechanisms of Early-Stage Bone Colonization of Breast CancerR01CA183878 · NCI · BAYLOR COLLEGE OF MEDICINE · PI ZHANG, XIANG · 2014 to 2024
$3.5MSpatiotemporal modeling of cancer-niche interactions in breast cancer bone metastasisU01CA253553 · NCI · METHODIST HOSPITAL RESEARCH INSTITUTE · PI WONG, STEPHEN TC, ZHANG, XIANG · 2020 to 2024
$3.0MUnveiling the mechanisms underlying secondary metastasis and possible therapeutic windowsR01CA251950 · NCI · BAYLOR COLLEGE OF MEDICINE · PI ZHANG, XIANG · 2020 to 2024
$2.6MOsteogenic Niche Biology in Progression and Endocrine Resistance of Bone MetastasesR01CA221946 · NCI · BAYLOR COLLEGE OF MEDICINE · PI ROWLEY, DAVID R · 2018 to 2022
$2.4MRewired Metabolism Regulates Vessel Normalization and ImmunosuppressionR01CA227904 · NCI · BAYLOR COLLEGE OF MEDICINE · PI SREEKUMAR, ARUN, ZHANG, XIANG · 2019 to 2023
$2.3MIdentify the DNA Adduct and Associated Metabolic Alterations in Bladder Cancer of SmokersR01CA216426 · NCI · BAYLOR COLLEGE OF MEDICINE · PI EL-ZEIN, RANDA A, PUTLURI, NAGIREDDY · 2018 to 2022
$2.0MRacial Disparity in Bladder Cancer and Identification of Altered Metabolism in African American Compare to European Bladder CancerR01CA220297 · NCI · BAYLOR COLLEGE OF MEDICINE · PI PUTLURI, NAGIREDDY · 2017 to 2021
$1.8MHigh Throughput Genomic Sequencer at BCM Core FacilityS10OD023469 · OD · BAYLOR COLLEGE OF MEDICINE · PI CHEN, RUI · 2017 to 2017
$600kHigh Memory High-Performance Computer Cluster for Biomedical ResearchS10OD032185 · OD · BAYLOR COLLEGE OF MEDICINE · PI HILSENBECK, SUSAN G. · 2022 to 2022
$596kNCI NIH HHS F31 CA281063NCI NIH HHS K99 CA279899NCI NIH HHS P30 CA125123NCI NIH HHS P50 CA186784NCI NIH HHS R01 CA183878NCI NIH HHS R01 CA216426NCI NIH HHS R01 CA220297NCI NIH HHS R01 CA221946NCI NIH HHS R01 CA227904NCI NIH HHS R01 CA251950NCI NIH HHS U01 CA253553NCRR NIH HHS S10 RR024574NEI NIH HHS P30 EY002520NIH HHS S10 OD023469NIH HHS S10 OD025240NIH HHS S10 OD032185
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.
Indexed as
Arachidonic AcidDrug Resistance, NeoplasmNeutrophilsTriple Negative Breast NeoplasmsAnimalsCell Line, TumorFemaleHumansImmune Checkpoint InhibitorsMiceProgrammed Cell Death 1 ReceptorTumor MicroenvironmentArachidonic AcidImmune Checkpoint InhibitorsProgrammed Cell Death 1 Receptorarachidonic acidextracellular vesiclesimmunotherapyneutrophilstriple negative breast cancer
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