{
  "abstract": "Triple-negative breast cancer (TNBC) is an aggressive, heterogeneous disease with limited targeted treatment options. Leveraging bulk and spatial transcriptomics and cellular mapping of breast tissue from a large patient cohort, we identified three reproducible TNBC ecosystem subtypes that encode distinct spatial tumor-microenvironment architectures and clinically relevant treatment-response phenotype. Our analyses define: (1) an immune-exhausted subtype associated with immune checkpoint therapy (ICT); (2) a highly fibrotic/hypoxic subtype; and (3) a metabolically reprogrammed subtype characterized by nuclear-receptor and fatty-acid signaling. Spatial profiling further revealed subtype-specific organization of epithelial, immune, and stromal programs across tumor centers and invasive edges. Multiplexed imaging independently supported the contrasting immune-infiltrated and stromal-excluded architectures of the immune-engaged and fibrotic subtypes. The unique markers associated with the subtypes also provide the basis for subtyping and candidate therapeutic vulnerabilities. Our study provides a robust framework for personalized medicine, highlighting that targeting specific spatio-cellular architectures is critical to improving clinical outcomes.",
  "abstract_shown": true,
  "affiliations": [
    "UC San Diego"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "name": "Z. Mesrizadeh"
    },
    {
      "name": "K. Mukund"
    },
    {
      "name": "L. Yang"
    },
    {
      "name": "R. K. Pillai"
    },
    {
      "name": "D. E. Frankhouser"
    },
    {
      "name": "D. Schmolze"
    },
    {
      "name": "S. L. Neuhausen"
    },
    {
      "name": "J. Zabaleta"
    },
    {
      "name": "L. D. Valle"
    },
    {
      "name": "J. Tomsic"
    },
    {
      "name": "Y. C. Ding"
    },
    {
      "name": "A. Ochoa"
    },
    {
      "name": "L. Miele"
    },
    {
      "name": "V. Seewaldt"
    },
    {
      "affs": [
        0
      ],
      "name": "S. Subramaniam"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5dygw7a55614g.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.10.758236",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.10.758236v1.full",
  "id": "5dygw7a55614g",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.10.758236v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cancer biology"
    ],
    [
      "openalex",
      "1306|Breast Cancer Treatment Studies"
    ]
  ],
  "openalex": "W7221681643",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.10.758236v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-10",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/5dygw7a55614g.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:27:33Z",
      "native_id": "10.64898/2026.10.10.758236",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.10.758236v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "Spatial context of cellular heterogeneity in triple-negative breast cancer reveals actionable subtypes",
  "title_text": "Spatial context of cellular heterogeneity in triple-negative breast cancer reveals actionable subtypes",
  "type": "preprint",
  "updated_at": "2026-10-30T12:27:33Z",
  "url": "https://research.draconitic.com/paper/5dygw7a55614g",
  "venue": "bioRxiv",
  "versions": []
}