{
  "abstract": "Metastatic dissemination is a major cause of mortality in triple-negative breast cancer (TNBC), yet how tumor metabolic state regulates immune surveillance during metastasis remains poorly understood. Here, we identify de novo lipogenesis as a tumor-intrinsic determinant of immune visibility and metastatic progression. Genetic or pharmacologic disruption of fatty acid synthase (FASN) suppresses metastasis with limited effects on primary tumor growth and enhances tumor-cell major histocompatibility complex class I (MHC-I) antigen presentation and CD8+ T cell activation. Mechanistically, FASN-dependent lipogenesis sustains epidermal growth factor receptor (EGFR) palmitoylation, selectively maintaining PI3K-AKT-mTOR signaling without altering EGFR abundance, cell-surface localization, or MAPK activation. Disruption of FASN-dependent lipogenesis, EGFR palmitoylation, or mTOR signaling restores peptide-MHC-I presentation and enhances antigen-specific CD8+ T cell recognition and cytotoxicity. FASN loss increases the abundance of multiple antigen-processing machinery proteins without corresponding changes in MHC-I transcript abundance, supporting transcription-independent regulation of antigen presentation downstream of PI3K-AKT-mTOR signaling. Tumor-cell B2M depletion substantially restores metastatic outgrowth and circulating tumor cells following FASN loss, identifying MHC-I antigen presentation as a major mediator of lipogenesis-dependent metastatic immune escape. In patient-derived TNBC organoids and independent human breast cancer cohorts, elevated lipogenic gene expression correlated with PI3K-AKT-mTOR-related transcriptional programs and reduced immune-surveillance programs, without significant differences in MHC-I transcriptional signatures. Together, these findings define a tumor-intrinsic immunometabolic circuit in which de novo lipogenesis sustains EGFR palmitoylation and PI3K-AKT-mTOR signaling to regulate antigen presentation, thereby modulating tumor-cell immune visibility during metastatic progression.",
  "abstract_shown": true,
  "affiliations": [
    "Weill Cornell Medicine of Cornell University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "name": "M. S. Ko"
    },
    {
      "name": "H. Withers"
    },
    {
      "name": "D. Ramchandani"
    },
    {
      "name": "J. McCormick"
    },
    {
      "name": "S. E. Carrasco"
    },
    {
      "name": "P. Amartey"
    },
    {
      "name": "A. Singh"
    },
    {
      "name": "L. Yoffe"
    },
    {
      "name": "G. E. Simmons"
    },
    {
      "name": "G. Zhang"
    },
    {
      "name": "W. H. Shen"
    },
    {
      "affs": [
        0
      ],
      "name": "V. Mittal"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4q6ytcxqa98c9.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.05.21.726063",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.05.21.726063v2.full",
  "id": "4q6ytcxqa98c9",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.05.21.726063v2",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cancer biology"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.05.21.726063v2.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-05-21",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/4q6ytcxqa98c9.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:28:55Z",
      "native_id": "10.64898/2026.05.21.726063",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.05.21.726063v4"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "De novo lipogenesis controls antigen presentation and metastatic immune escape in triple-negative breast cancer.",
  "title_text": "De novo lipogenesis controls antigen presentation and metastatic immune escape in triple-negative breast cancer.",
  "type": "preprint",
  "updated_at": "2026-11-01T00:21:30Z",
  "url": "https://research.draconitic.com/paper/4q6ytcxqa98c9",
  "venue": "bioRxiv",
  "versions": []
}