{
  "abstract": "Immune-active hepatocellular carcinoma (HCC) is commonly treated as a single inflamed phenotype, although its internal immune heterogeneity remains incompletely defined. We integrated public bulk transcriptomic, single-cell, spatial transcriptomic, proteomic, phosphoproteomic, and treatment-cohort data to test whether this heterogeneity is better represented by discrete states or a continuous immune axis. In 112 checkpoint-high TCGA-LIHC tumors, an inflamed-minus-myeloid axis showed structured heterogeneity but no robust empirical bimodality: the observed kernel-density curve had one prominent mode and none of 1,000 bootstrap resamples contained two or more prominent modes. IFNγ-responsive-associated and myeloid-suppressive-associated labels were therefore retained only as operational summaries of opposing axis tendencies, and the biological polarity persisted across alternative definitions of immune-active entry. A fixed 10-gene within-sample rank template-contrast score transferred the axis to independent HCC cohorts. Transcriptomic analyses based on gene sets non-overlapping with the compact panel and original state-defining genes supported the IFNγ-oriented end, whereas spatial analyses showed local cross-end coexistence with reduced immediate-neighbor mixing relative to a count-preserving random-label null, and paired proteomic/phosphoproteomic analyses showed concordant myeloid-oriented associations involving macrophage, fibroblast/extracellular-matrix, hypoxia, SPP1-integrin-FAK, and myeloid-receptor programs. Direct application of the frozen transfer score to four public HCC immunotherapy cohorts yielded heterogeneous, imprecise response associations (pooled Hedges’ g = 0.10, 95% CI −0.42 to 0.61) and did not establish clinical response prediction. These results support a structured IFNγ-responsive-to-myeloid-suppressive continuum within immune-active HCC. The framework is transferable across public datasets but requires prospective HCC-specific clinical validation, while functional perturbation studies are needed before causal or therapeutic claims.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Hepatobiliary and Pancreatic Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China",
    "Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
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        0
      ],
      "name": "Luping Lin"
    },
    {
      "affs": [
        1
      ],
      "name": "Ningna Weng"
    },
    {
      "name": "Huaying Lai"
    },
    {
      "name": "Guangfeng Wu"
    },
    {
      "name": "Jinfeng Lin"
    },
    {
      "name": "Xinjian Wu"
    },
    {
      "name": "Sha Huang"
    },
    {
      "name": "Xiao Chen"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e4gm3rxtnn5p3.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pone.0359327",
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  "id": "e4gm3rxtnn5p3",
  "issns": [
    "1932-6203"
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  "landing_url": "https://doi.org/10.1371/journal.pone.0359327",
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  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
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  "native_subjects": [
    [
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      "2730|Cancer Immunotherapy and Biomarkers"
    ],
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      "/Biology and life sciences/Biochemistry/Proteins/Immune system proteins/Complement system"
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      "/Medicine and health sciences/Clinical medicine/Clinical immunology/Immunotherapy"
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      "/Medicine and health sciences/Gastroenterology and hepatology/Liver diseases/Hepatocellular carcinoma"
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      "/Medicine and health sciences/Immunology/Immune response"
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      "/Medicine and health sciences/Immunology/Immune system proteins/Complement system"
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      "/Medicine and health sciences/Immunology/Immune system/Complement system"
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      "/Medicine and health sciences/Oncology/Cancer treatment"
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      "/Medicine and health sciences/Oncology/Cancers and neoplasms"
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    [
      "plos",
      "/Medicine and health sciences/Oncology/Cancers and neoplasms/Carcinoma/Hepatocellular carcinoma"
    ],
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      "plos",
      "/Medicine and health sciences/Oncology/Cancers and neoplasms/Gastrointestinal tumors/Hepatocellular carcinoma"
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  "openalex": "W7220653415",
  "pdf_url": "https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0359327&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-06",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/e4gm3rxtnn5p3.ris",
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    {
      "first_seen": "2026-10-30T12:17:30Z",
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  "subjects": [
    {
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      "origin": "plos:immunology",
      "subfield": "immunology"
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      "field": "medicine",
      "origin": "plos:oncology",
      "subfield": "oncology"
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  "title": "Integrated multi-omic analysis characterizes an IFNγ-responsive-to-myeloid-suppressive immune continuum in immune-active hepatocellular carcinoma",
  "title_text": "Integrated multi-omic analysis characterizes an IFNγ-responsive-to-myeloid-suppressive immune continuum in immune-active hepatocellular carcinoma",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:36Z",
  "url": "https://research.draconitic.com/paper/e4gm3rxtnn5p3",
  "venue": "PLOS One",
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}