{
  "abstract": "Triple-negative breast cancer (TNBC) develops in hypoxic, nutrient-limited tumors enriched with macrophages and cell death. We show that metabolically distinct TNBCs differentially exploit macrophage-derived nutrients, influencing tumor growth and therapeutic response. Prolonged hypoxia reprogrammed mouse and human macrophages, enabling them to release metabolites that rescued the growth of select TNBC cell lines during glutamine deprivation or glutamine metabolism inhibition. Hypoxic macrophages reduced glutamine consumption, increased arginine utilization, and secreted higher levels of ornithine, an intermediate of arginine metabolism. Exogenous ornithine, but not arginine, restored the growth of responsive TNBC cells. Mechanistically, TNBC cells diverted ornithine into proline biosynthesis, supporting oxidative pentose phosphate pathway activity. In vivo, depletion of tumor-associated myeloid cells reduced tumor growth and impaired proline synthesis in glutaminase inhibitor-resistant TNBC. These findings identify hypoxia-driven metabolic cross-talk between macrophages and TNBC cells, revealing ornithine-dependent proline metabolism as a mechanism by which macrophages sustain tumor growth under nutrient stress and contribute to resistance to glutamine-targeted therapies.",
  "abstract_shown": true,
  "affiliations": [
    "Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.",
    "Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.",
    "Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.",
    "Computational Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.",
    "Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, USA.",
    "The Donald B. and Catherine C. Marron Cancer Metabolism Center, Memorial Sloan Kettering Cancer Center, New York, NY, USA.",
    "Pat and Ian Cook Doctoral Program in Cancer Engineering, Memorial Sloan Kettering Cancer Center, New York, NY, USA.",
    "Department of Immunology and Microbial Pathogenesis, Weill Cornell Medical College, New York, NY, USA."
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 18,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Nancy T. Santiappillai",
      "orcid": "0000-0001-9797-559X"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Andrew Cho",
      "orcid": "0000-0002-5396-5354"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Georg Verch",
      "orcid": "0009-0002-9088-0111"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Ana C. Codo",
      "orcid": "0000-0001-9036-5772"
    },
    {
      "affs": [
        2,
        4
      ],
      "name": "Achuth Nair",
      "orcid": "0009-0003-2933-3490"
    },
    {
      "affs": [
        2
      ],
      "name": "Ya-Ting Wang",
      "orcid": "0000-0003-1101-5438"
    },
    {
      "affs": [
        2
      ],
      "name": "Allie Lipshutz",
      "orcid": "0000-0002-1786-7300"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Celia Martínez de la Torre",
      "orcid": "0000-0002-5088-3839"
    },
    {
      "affs": [
        3
      ],
      "name": "Eric Minwei Liu",
      "orcid": "0000-0002-3594-6678"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Marjan Berishaj"
    },
    {
      "affs": [
        2
      ],
      "name": "Alissa J. Trzeciak",
      "orcid": "0000-0002-4518-0098"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Zhaoquan Wang",
      "orcid": "0000-0001-8227-0941"
    },
    {
      "affs": [
        5
      ],
      "name": "Michelle Saoi",
      "orcid": "0000-0001-7678-6239"
    },
    {
      "affs": [
        2
      ],
      "name": "Waleska Saitz Rojas",
      "orcid": "0000-0003-0186-1980"
    },
    {
      "affs": [
        5
      ],
      "name": "Justin R. Cross"
    },
    {
      "affs": [
        3,
        4,
        6
      ],
      "name": "Ed Reznik",
      "orcid": "0000-0002-6511-5947"
    },
    {
      "affs": [
        2,
        4,
        6,
        7
      ],
      "name": "Justin S. A. Perry",
      "orcid": "0000-0003-4063-6524"
    },
    {
      "affs": [
        0,
        1,
        4,
        6
      ],
      "name": "Kayvan R. Keshari",
      "orcid": "0000-0002-5181-8035"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9x52r742jngb5.bib",
  "cited_by": 0,
  "doi": "10.1126/sciadv.aei2831",
  "fulltext_url": null,
  "id": "9x52r742jngb5",
  "issns": [
    "2375-2548"
  ],
  "landing_url": "https://www.science.org/doi/10.1126/sciadv.aei2831",
  "language": null,
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2403|Immune cells in cancer"
    ]
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  "openalex": "W7214037269",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-02",
  "publisher": "American Association for the Advancement of Science (AAAS)",
  "ris": "https://research.draconitic.com/paper/9x52r742jngb5.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:41Z",
      "native_id": "10.1126/sciadv.aei2831",
      "source": "crossref",
      "url": "https://www.science.org/doi/10.1126/sciadv.aei2831"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Immune cells in cancer",
      "subfield": "immunology"
    }
  ],
  "title": "Macrophage-supported metabolic adaptation drives tumor survival under nutrient stress",
  "title_text": "Macrophage-supported metabolic adaptation drives tumor survival under nutrient stress",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:41Z",
  "url": "https://research.draconitic.com/paper/9x52r742jngb5",
  "venue": "Science Advances",
  "versions": []
}