{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T20:29:51Z","timestamp":1793737791591,"version":"4.6.1"},"posted":{"date-parts":[[2026,5,26]]},"group-title":"Cancer Biology","reference-count":53,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH Common Fund","award":["R01 CA257254-01A1"],"award-info":[{"award-number":["R01 CA257254-01A1"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"crossref"}]},{"name":"NIH Common Fund","award":["1S10OD032397-01A1"],"award-info":[{"award-number":["1S10OD032397-01A1"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"crossref"}]},{"name":"NIH Common Fund","award":["U24CA274159"],"award-info":[{"award-number":["U24CA274159"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"crossref"}]},{"name":"NIH Common Fund","award":["W81XWH-21-2-0031"],"award-info":[{"award-number":["W81XWH-21-2-0031"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,10,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  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\n                  <jats:sup>+<\/jats:sup>\n                  T cell activation. Mechanistically, FASN-dependent lipogenesis sustains epidermal growth factor receptor (EGFR) palmitoylation, selectively maintaining PI3K\u2212AKT\u2212mTOR signaling without altering EGFR abundance, cell-surface localization, or MAPK activation. Disruption of FASN-dependent lipogenesis, EGFR palmitoylation, or mTOR signaling restores peptide\u2013MHC-I presentation and enhances antigen-specific CD8\n                  <jats:sup>+<\/jats:sup>\n                  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\u2212AKT\u2212mTOR 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\u2212AKT\u2212mTOR-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\u2212AKT\u2212mTOR signaling to regulate antigen presentation, thereby modulating tumor-cell immune visibility during metastatic progression.\n                <\/jats:p>","DOI":"10.64898\/2026.05.21.726063","type":"posted-content","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T18:05:17Z","timestamp":1779818717000},"source":"Crossref","is-referenced-by-count":0,"title":["De novo lipogenesis controls antigen presentation and metastatic immune escape in triple-negative breast cancer"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0053-3697","authenticated-orcid":false,"given":"Myung Soo","family":"Ko","sequence":"first","affiliation":[{"name":"Department of Cardiothoracic Surgery, Weill Cornell Medicine, New York, NY, USA"},{"name":"Neuberger Berman Lung Cancer Center, Weill Cornell Medicine, New York, NY, 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Cancer Center, Weill Cornell Medicine, Rockefeller University, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pius","family":"Amartey","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arshdeep","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, Weill Cornell Medicine, New York, NY, USA"},{"name":"Neuberger Berman Lung Cancer Center, Weill Cornell Medicine, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3040-8205","authenticated-orcid":false,"given":"Liron","family":"Yoffe","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, Weill Cornell Medicine, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Glenn E.","family":"Simmons","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Proteomics and Metabolomics Core Facility, Weill Cornell Medicine, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen H.","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Weill Cornell Medicine, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivek","family":"Mittal","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, Weill Cornell Medicine, New York, NY, USA"},{"name":"Neuberger Berman Lung Cancer Center, Weill Cornell Medicine, New York, NY, 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