{
  "abstract": "Background and aims: Hepatocellular carcinoma (HCC) has a spatially heterogeneous immune microenvironment, but the compartment-specific distribution of tumor-associated neutrophils (TANs) and its relationship with systemic inflammation remain incompletely defined. This study characterized CD177-defined neutrophil populations and other immune components across HCC tissue compartments and examined their associations with peripheral neutrophil-to-lymphocyte ratio (NLR).\n\nMethods: Paired tumor center (TC), tumor margin/interface (IM), and adjacent non-neoplastic liver (NNL) specimens from 28 patients with HCC were analyzed using immunofluorescence microscopy and quantitative immunohistochemistry. Total neutrophil elastase-positive (NE ⁺ ) and CD177 ⁺ NE ⁺ neutrophils, CD8 ⁺ lymphocytes, CD68 ⁺ and CD163 ⁺ macrophages, and CD34 ⁺ microvascular density were quantified.\n\nResults: Total NE ⁺ neutrophil density differed across compartments and was higher in both tumor-associated compartments than in NNL (median: TC, 46.40 cells/mm²; IM, 39.65 cells/mm²; NNL, 8.80 cells/mm²; P < 0.001). CD177 ⁺ NE ⁺ density showed a modest compartmental effect and was higher in the TC than at the IM (RR 2.68, 95% CI 1.20–6.02; Holm-adjusted P = 0.050). In contrast, the CD177 ⁺ fraction among total NE ⁺ neutrophils was markedly lower in both tumor-associated compartments than in NNL (median: TC, 17.63%; IM, 10.90%; NNL, 88.08%; P < 0.001)among, accompanied by substantial enrichment of estimated NE ⁺ CD177 ⁻ neutrophils. CD8 ⁺ lymphocytes preferentially accumulated at the IM, whereas CD34 ⁺ microvascular density followed a TC>IM>NNL gradient. CD68 ⁺ macrophages were more abundant in NNL, while CD163 ⁺ macrophage density showed a modest overall compartment effect (mixed-effects P = 0.037), and the CD163/CD68 macrophage-polarization index was higher in the TC than at the IM ( P = 0.009). In exploratory analyses, higher preoperative NLR was associated with the CD163/CD68 macrophage-polarization index specifically in the TC (ρ = 0.451, P = 0.016; q = 0.048), but not with neutrophil abundance, CD177-defined distribution, or patient-level neutrophil spatial-distribution indices.\n\nConclusions: HCC exhibits marked spatial myeloid heterogeneity, characterized by neutrophil enrichment in tumor-associated compartments, compartmental differences in CD177-defined populations, and compartment-specific macrophage polarization. These findings, generated using a practical tissue-based immunophenotyping approach applicable to routinely processed specimens, warrant validation in larger mechanistic studies.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Gastroenterology and Hepatology, First Department of Internal Medicine, AHEPA University Hospital, Aristotle University of Thessaloniki",
    "Department of Pathology, School of Medicine, Aristotle University of Thessaloniki",
    "Laboratory of Anatomy, Medical School, Democritus University of Thrace",
    "Department of Physiology, Medical School, National and Kapodistrian University of Athens",
    "Department of Transplantation Surgery, Hippokration General Hospital, School of Medicine, Aristotle University of Thessaloniki",
    "Laboratory of Molecular Hematology, Democritus University of Thrace",
    "Department of Pathology, Democritus University of Thrace",
    "Department of Pathology, Hippokration General Hospital, School of Medicine, Aristotle University of Thessaloniki"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Konstantinos Arvanitakis"
    },
    {
      "affs": [
        1
      ],
      "name": "Christos Topalidis"
    },
    {
      "affs": [
        2
      ],
      "name": "Vasileios Papadopoulos"
    },
    {
      "affs": [
        3
      ],
      "name": "Eirini Giannousi"
    },
    {
      "affs": [
        0
      ],
      "name": "Georgios Kalopitas"
    },
    {
      "affs": [
        3
      ],
      "name": "Antonios Chatzigeorgiou"
    },
    {
      "affs": [
        4
      ],
      "name": "Georgios Katsanos"
    },
    {
      "affs": [
        5
      ],
      "name": "Anastasia Maria Natsi"
    },
    {
      "affs": [
        5
      ],
      "name": "Ioannis Mitroulis"
    },
    {
      "affs": [
        6
      ],
      "name": "Stella Arelaki"
    },
    {
      "affs": [
        7
      ],
      "name": "Chrysoula Gouta"
    },
    {
      "affs": [
        7
      ],
      "name": "Evangelia Katsiki"
    },
    {
      "affs": [
        1
      ],
      "name": "Prodromos Hytiroglou"
    },
    {
      "affs": [
        4
      ],
      "name": "Georgios Tsoulfas"
    },
    {
      "affs": [
        1
      ],
      "name": "Triantafyllia Koletsa"
    },
    {
      "affs": [
        0
      ],
      "name": "Georgios Germanidis"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1qy2mep636jmg.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1982507",
  "fulltext_url": "https://europepmc.org/articles/PMC13683775",
  "id": "1qy2mep636jmg",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1982507/full",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2403|Immune cells in cancer"
    ]
  ],
  "openalex": "W7220845055",
  "pdf_url": "https://europepmc.org/articles/PMC13683775?pdf=render",
  "pmcid": "PMC13683775",
  "pmid": "42909139",
  "published": "2026-10-07",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/1qy2mep636jmg.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:15Z",
      "native_id": "10.3389/fimmu.2026.1982507",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1982507/full"
    },
    {
      "first_seen": "2026-10-30T12:20:10Z",
      "native_id": "MED:42909139",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42909139"
    }
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  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Immune cells in cancer",
      "subfield": "immunology"
    }
  ],
  "title": "Spatial organization of neutrophil and macrophage populations in surgically treated hepatocellular carcinoma: a practical tissue-based immunophenotyping study",
  "title_text": "Spatial organization of neutrophil and macrophage populations in surgically treated hepatocellular carcinoma: a practical tissue-based immunophenotyping study",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:10Z",
  "url": "https://research.draconitic.com/paper/1qy2mep636jmg",
  "venue": "Frontiers in Immunology",
  "versions": []
}