{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:50:18Z","timestamp":1791355818268,"version":"4.3.1"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"\n Background and aims<\/jats:title>\n 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).<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n 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\n +<\/jats:sup>\n ) and CD177\n +<\/jats:sup>\n NE\n +<\/jats:sup>\n neutrophils, CD8\n +<\/jats:sup>\n lymphocytes, CD68\n +<\/jats:sup>\n and CD163\n +<\/jats:sup>\n macrophages, and CD34\n +<\/jats:sup>\n microvascular density were quantified.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Total NE\n +<\/jats:sup>\n neutrophil density differed across compartments and was higher in both tumor-associated compartments than in NNL (median: TC, 46.40 cells\/mm\u00b2; IM, 39.65 cells\/mm\u00b2; NNL, 8.80 cells\/mm\u00b2;\n P<\/jats:italic>\n \u00a0&lt;\u00a00.001). CD177\n +<\/jats:sup>\n NE\n +<\/jats:sup>\n density showed a modest compartmental effect and was higher in the TC than at the IM (RR 2.68, 95% CI 1.20\u20136.02; Holm-adjusted\n P<\/jats:italic>\n \u00a0=\u00a00.050). In contrast, the CD177\n +<\/jats:sup>\n fraction among total NE\n +<\/jats:sup>\n neutrophils was markedly lower in both tumor-associated compartments than in NNL (median: TC, 17.63%; IM, 10.90%; NNL, 88.08%;\n P<\/jats:italic>\n \u00a0&lt;\u00a00.001)among, accompanied by substantial enrichment of estimated NE\n +<\/jats:sup>\n CD177\n -<\/jats:sup>\n neutrophils. CD8\n +<\/jats:sup>\n lymphocytes preferentially accumulated at the IM, whereas CD34\n +<\/jats:sup>\n microvascular density followed a TC&gt;IM&gt;NNL gradient. CD68\n +<\/jats:sup>\n macrophages were more abundant in NNL, while CD163\n +<\/jats:sup>\n macrophage density showed a modest overall compartment effect (mixed-effects\n P<\/jats:italic>\n \u00a0=\u00a00.037), and the CD163\/CD68 macrophage-polarization index was higher in the TC than at the IM (\n P<\/jats:italic>\n \u00a0=\u00a00.009). In exploratory analyses, higher preoperative NLR was associated with the CD163\/CD68 macrophage-polarization index specifically in the TC (\u03c1 = 0.451,\n P<\/jats:italic>\n = 0.016; q = 0.048), but not with neutrophil abundance, CD177-defined distribution, or patient-level neutrophil spatial-distribution indices.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1982507","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:58:41Z","timestamp":1791352721000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Spatial organization of neutrophil and macrophage populations in surgically treated hepatocellular carcinoma: a practical tissue-based immunophenotyping study"],"prefix":"10.3389","volume":"17","author":[{"given":"Konstantinos","family":"Arvanitakis","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, First Department of Internal Medicine, AHEPA University Hospital, Aristotle University of Thessaloniki","place":["Thessaloniki, 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