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Here, we identify the mitochondrial carnitine\u2010acylcarnitine translocase solute carrier 25 member 20 (SLC25A20), an essential conduit for FAO, as a key regulator of CRC progression through neutrophil phenotypic remodel. Mechanistically, SLC25A20 deficiency in CRC cells blunts mitochondrial long\u2010chain fatty acid (LCFA) import and FAO, triggering the release of LCFAs into the TME. This lipid\u2010rich niche not only vigorously recruits tumor\u2010associated neutrophils (TANs), but intrinsically programs them toward an immunosuppressive phenotype. Specifically, tumor\u2010derived LCFAs enforce arginase\u20101 (ARG1) protein stability in TANs via ZDHHC18\u2010mediated palmitoylation. This distinct post\u2010translational modification (PTM) is indispensable for TAN\u2010mediated CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell suppression and subsequent tumor immune evasion. Importantly, genetic or pharmacological blockade of this palmitoylation axis in TANs reinvigorates antitumor immunity and abolishes the tumor\u2010promoting effects of SLC25A20 deficiency. Collectively, our findings uncover a novel lipid\u2010driven metabolic symbiosis between CRC and neutrophils, highlighting the ZDHHC18\u2010ARG1 palmitoylation axis as a promising therapeutic strategy for CRC intervention.\n                  <\/jats:p>","DOI":"10.1002\/advs.78114","type":"journal-article","created":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T16:11:27Z","timestamp":1791130287000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Epithelial SLC25A20 Deficiency Drives Immunosuppressive Neutrophil Remodeling via ARG1 Palmitoylation to Promote Colorectal Cancer"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4559-1502","authenticated-orcid":false,"given":"Yue","family":"Han","sequence":"first","affiliation":[{"name":"Department of Pathology, Nanfang Hospital, School of Basic Medical Sciences Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian\u2010Yuan","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Pathology, Nanfang Hospital, School of Basic Medical Sciences Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Nanfang Hospital, School of Basic Medical Sciences Southern Medical University  Guangzhou China"},{"name":"Department of Pathology, Zhujiang Hospital Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1133-9810","authenticated-orcid":false,"given":"Ye\u2010Bin","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Nanfang Hospital, School of Basic Medical Sciences Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0986-3184","authenticated-orcid":false,"given":"Wen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Nanfang Hospital, School of Basic Medical Sciences Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min\u2010Hui","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Nanfang Hospital, School of Basic Medical Sciences Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8246-6626","authenticated-orcid":false,"given":"Yi\u2010Qing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Nanfang Hospital, School of Basic Medical Sciences Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan\u2010Qing","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Pathology, Nanfang Hospital, School of Basic Medical Sciences Southern Medical University  Guangzhou China"},{"name":"Guangdong Province Key Laboratory of Molecular Tumor Pathology  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0811-0696","authenticated-orcid":false,"given":"Shuang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Nanfang Hospital, School of Basic Medical Sciences Southern Medical University  Guangzhou China"},{"name":"Department of Pathology, Zhujiang Hospital Southern Medical University  Guangzhou China"},{"name":"Guangdong Province Key Laboratory of Molecular Tumor Pathology  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,4]]},"reference":[{"issue":"1","key":"e_1_2_10_2_1","first-page":"17","article-title":"Cancer statistics","volume":"73","author":"Siegel R. 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