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Adv."],"published-print":{"date-parts":[[2026,10,9]]},"abstract":"<jats:p>\n                    Tumor metabolic programs shape immune evasion; however, the mechanism by which nutrient-transport systems rewire tumor-immune cell interactions remains unknown. We integrated bulk multi-omics, single-cell transcriptomics, spatial profiling, and functional assays for colorectal cancer\u2013associated zinc-driven immunosuppressive circuit identification. Multi-omics analysis of 258 patients revealed three solute carrier transporter-centered archetypes, with an SLC39-enriched subtype aligned with consensus molecular subtype 2\u2013like immune-desert tumors. SLC39-mediated zinc influx activated CDX2, which engaged a distal enhancer to induce tumor cell-specific CD24 expression. CD24\n                    <jats:sup>+<\/jats:sup>\n                    tumor cells formed spatial niches with SIGLEC10-expressing monocyte-derived macrophages, dendritic cells, and resident macrophages, activating pleiotropic programs that suppress phagocytosis and remodel adhesion. SLC39 overexpression increased intracellular zinc and CD24 levels and reduced macrophage-mediated engulfment, whereas CD24 blockade restored phagocytosis. The zinc-CDX2-CD24-SIGLEC10 axis defined a terminal cancer cell state associated with poor survival and immune checkpoint blockade resistance. A seven-gene signature predicted immunotherapy responses across five colorectal cancer cohorts, identifying SLC39-driven zinc influx as a metabolic checkpoint governing immune exclusion.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aeh2362","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T17:58:33Z","timestamp":1791395913000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["SLC39-driven zinc influx orchestrates pleiotropic tumor\u2013immune system cross-talk to establish immune suppression in colorectal cancer"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-7364-9756","authenticated-orcid":true,"given":"Seok June","family":"Hong","sequence":"first","affiliation":[{"name":"Department of Biomedical and Pharmaceutical Sciences, Kyung Hee University, Seoul, Republic of 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