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Tumor cells reprogram their metabolism to evade immune surveillance, a critical step to achieving metastatic outgrowth. Using an unbiased CRISPR screen targeting metabolism-related genes and a clinically relevant spontaneous metastasis mouse model, we identified CPT1A, the rate-limiting enzyme in fatty acid \u03b2-oxidation, as a suppressor of immune-dependent metastasis. Loss of CPT1A enhances lung metastasis in immunocompetent mice, but not Rag1 KO mice that lack mature lymphocytes. Loss of CPT1A triggers cytosolic mitochondrial DNA (mtDNA) release via the mPTP pore. Cytosolic mtDNA release triggers a STING-dependent inflammatory response, creating an environment that impairs CD8+ T cell function, promoting metastatic outgrowth. Among breast cancer patients, low\n                  <jats:italic>CPT1A<\/jats:italic>\n                  expression correlates with poor survival when CD8+ T cell infiltration is high. These findings reveal an extrinsic role for CPT1A in immune-tumor dynamics and suggest therapeutic opportunities targeting inflammation in metastatic breast cancer.\n                <\/jats:p>","DOI":"10.64898\/2026.05.01.722261","type":"posted-content","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T07:00:26Z","timestamp":1778050826000},"source":"Crossref","is-referenced-by-count":0,"title":["CPT1A loss promotes lung metastasis in immune-competent mice via a mechanism of mtDNA release and chronic activation of STING pathway"],"prefix":"10.64898","author":[{"given":"Xiaoyong","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Rheumatology and Immunology, Vanderbilt Health, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Ting","family":"Chou","sequence":"additional","affiliation":[{"name":"Program in Cancer Biology, Vanderbilt University, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoonha","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Rheumatology and Immunology, Vanderbilt Health, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Rheumatology and Immunology, Vanderbilt Health, Nashville, Tennessee, USA"},{"name":"Program in Cancer Biology, Vanderbilt University, Nashville, Tennessee, USA"},{"name":"Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, USA"},{"name":"Vanderbilt Institute for Infection, Immunology, and Inflammation, Nashville, Tennessee, USA"},{"name":"Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deanna N.","family":"Edwards","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Rheumatology and Immunology, Vanderbilt Health, Nashville, Tennessee, USA"},{"name":"Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026050819401003000_2026.05.01.722261v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2023.02.018"},{"key":"2026050819401003000_2026.05.01.722261v1.2","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1007\/s12094-022-02950-4","article-title":"The pro-tumorigenic responses in metastatic niches: an immunological perspective","volume":"25","year":"2022","journal-title":"Clin Transl Oncol"},{"key":"2026050819401003000_2026.05.01.722261v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2025.05.006"},{"key":"2026050819401003000_2026.05.01.722261v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-023-00836-2"},{"key":"2026050819401003000_2026.05.01.722261v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/nri3789"},{"key":"2026050819401003000_2026.05.01.722261v1.6","doi-asserted-by":"crossref","first-page":"3447","DOI":"10.1038\/s41388-023-02868-3","article-title":"Metabolic control of cancer metastasis: role of amino acids at secondary organ sites","volume":"42","year":"2023","journal-title":"Oncogene"},{"key":"2026050819401003000_2026.05.01.722261v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-020-00320-2"},{"key":"2026050819401003000_2026.05.01.722261v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2018.04.002"},{"key":"2026050819401003000_2026.05.01.722261v1.9","doi-asserted-by":"publisher","DOI":"10.1158\/1538-7445.SABCS18-4003"},{"key":"2026050819401003000_2026.05.01.722261v1.10","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-019-0650-z"},{"key":"2026050819401003000_2026.05.01.722261v1.11","doi-asserted-by":"crossref","unstructured":"Jariwala, N. et al. 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