{
  "abstract": "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–associated 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–like immune-desert tumors. SLC39-mediated zinc influx activated CDX2, which engaged a distal enhancer to induce tumor cell-specific CD24 expression. CD24 + 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.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Biomedical and Pharmaceutical Sciences, Kyung Hee University, Seoul, Republic of Korea.",
    "School of Biosystems and Biomedical Sciences, College of Health Sciences, Korea University, Seoul 02841, Republic of Korea.",
    "Department of Integrated Biomedical and Life Sciences, College of Health Sciences, Korea University, Seoul 02841, Republic of Korea.",
    "L-HOPE Program for Community-Based Total Learning Health Systems, Korea University, Seoul 02841, Republic of Korea.",
    "Department of Health and Safety Convergence Science, College of Health Sciences, Korea University, Seoul 02841, Republic of Korea.",
    "School of Health and Environmental Science, College of Health Science, Korea University, Seoul 02841, Republic of Korea.",
    "Department of Health and Safety Convergence Science, College of Health Science, Korea University, Seoul 02841, Republic of Korea.",
    "Biomedical Research Center, Korea University Guro Hospital, Seoul 08308, Republic of Korea.",
    "Interdisciplinary Program in Precision Public Health, Korea University, Seoul 02841, Republic of Korea.",
    "Center of Molecular and Cellular Oncology, Yale University, New Haven, CT 06511, USA.",
    "Gene Lay Institute of Immunology and Inflammation, Brigham and Women’s Hospital, Harvard Medical School and Massachusetts General Hospital, Boston, MA 02115, USA.",
    "Department of Biology, Kyung Hee University, Seoul, Republic of Korea."
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Seok June Hong",
      "orcid": "0009-0004-7364-9756"
    },
    {
      "affs": [
        1,
        2,
        3
      ],
      "name": "Seheum Park",
      "orcid": "0009-0001-7065-2616"
    },
    {
      "affs": [
        1,
        2,
        3
      ],
      "name": "Sunghoon Kim"
    },
    {
      "affs": [
        1
      ],
      "name": "Young Il Park",
      "orcid": "0009-0009-7336-6584"
    },
    {
      "affs": [
        4
      ],
      "name": "Jun Seok Lee",
      "orcid": "0009-0006-6830-1338"
    },
    {
      "affs": [
        5,
        6,
        7
      ],
      "name": "Mikyung Kang",
      "orcid": "0000-0002-0592-1648"
    },
    {
      "affs": [
        1,
        2,
        8,
        9
      ],
      "name": "Jaewoong Lee"
    },
    {
      "affs": [
        10
      ],
      "name": "Martin Hemberg",
      "orcid": "0000-0001-8895-5239"
    },
    {
      "affs": [
        1,
        2,
        7
      ],
      "name": "Sung Eun Kim",
      "orcid": "0000-0002-4281-5625"
    },
    {
      "affs": [
        0,
        11
      ],
      "name": "Kwoneel Kim",
      "orcid": "0000-0002-4221-3421"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/14qapn62m9a7j.bib",
  "cited_by": 0,
  "doi": "10.1126/sciadv.aeh2362",
  "fulltext_url": null,
  "id": "14qapn62m9a7j",
  "issns": [
    "2375-2548"
  ],
  "landing_url": "https://www.science.org/doi/10.1126/sciadv.aeh2362",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2730|Cancer Immunotherapy and Biomarkers"
    ]
  ],
  "openalex": "W7220845577",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-09",
  "publisher": "American Association for the Advancement of Science (AAAS)",
  "ris": "https://research.draconitic.com/paper/14qapn62m9a7j.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:41Z",
      "native_id": "10.1126/sciadv.aeh2362",
      "source": "crossref",
      "url": "https://www.science.org/doi/10.1126/sciadv.aeh2362"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cancer Immunotherapy and Biomarkers",
      "subfield": "oncology"
    }
  ],
  "title": "SLC39-driven zinc influx orchestrates pleiotropic tumor–immune system cross-talk to establish immune suppression in colorectal cancer",
  "title_text": "SLC39-driven zinc influx orchestrates pleiotropic tumor–immune system cross-talk to establish immune suppression in colorectal cancer",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:41Z",
  "url": "https://research.draconitic.com/paper/14qapn62m9a7j",
  "venue": "Science Advances",
  "versions": []
}