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Overcoming the immune microenvironment in HCC remains a challenge, and innate immune populations such as tumour\u2010associated neutrophils can potentially impair the success of immunotherapy. Elucidating the mechanisms of neutrophil recruitment across liver endothelium could lead to new approaches to boost the efficacy of immunotherapy. CLEC14A is an endothelium\u2010specific receptor regulating sprouting angiogenesis, upregulated in low shear environments. We found CLEC14A to be highly expressed in both HCC vessels and on vasculature during acute liver injury, leading us to hypothesise that CLEC14A may regulate neutrophil recruitment to the liver and HCC. We found that CLEC14A positively correlated with a neutrophil signature and infiltration in public datasets and surgically resected tissue from HCC. Spatial transcriptomics (ST) of CLEC14A\n                    <jats:sup>high<\/jats:sup>\n                    \u2010 and CLEC14A\n                    <jats:sup>low<\/jats:sup>\n                    \u2010expressing tumours confirmed upregulation of myeloperoxidase in CLEC14A\n                    <jats:sup>high<\/jats:sup>\n                    tumours and correlation with other shear\u2010dependent markers but a negative correlation with vascular endothelial growth factor A. To build on our correlation studies, we explored the role of CLEC14A in neutrophil recruitment across liver endothelium. We undertook\n                    <jats:italic>in vitro<\/jats:italic>\n                    recruitment studies with flow\u2010based human liver endothelial assays and\n                    <jats:italic>in vivo<\/jats:italic>\n                    models of neutrophil recruitment. Using siRNA knockdown of\n                    <jats:italic>CLEC14A<\/jats:italic>\n                    and specific blocking antibodies to CLEC14A, we found that\n                    <jats:italic>CLEC14A<\/jats:italic>\n                    knockdown blocked the firm adhesion of neutrophils to liver endothelium, but this was independent of its interaction with its known ligand MMRN2. Finally, we confirmed that\n                    <jats:italic>Clec14a<\/jats:italic>\n                    deficiency led to a significant reduction in neutrophil recruitment across the sinusoids in an ischaemia\u2010reperfusion liver injury model. We unveil a link between the angiogenic receptor CLEC14A and neutrophil recruitment. Targeting of CLEC14A on tumour endothelium is potentially a new approach to regulating neutrophil infiltration in HCC. \u00a9 2026 The Author(s).\n                    <jats:italic>The Journal of Pathology<\/jats:italic>\n                    published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.70077","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T12:32:04Z","timestamp":1780317124000},"page":"478-492","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>CLEC14A<\/scp>\n                    correlates with neutrophil infiltration in hepatocellular carcinoma and mediates neutrophil recruitment across liver endothelial cells"],"prefix":"10.1002","volume":"269","author":[{"given":"Joanne M","family":"O'Rourke","sequence":"first","affiliation":[{"name":"Centre for Liver and Gastrointestinal Research, Department of Immunology and Immunotherapy, College of Medicine and Health University of Birmingham  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean","family":"Kavanagh","sequence":"additional","affiliation":[{"name":"Microcirculation Research Group, Department of Cardiovascular Sciences, College of Medicine and Health University of Birmingham  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayla","family":"O'Keeffe","sequence":"additional","affiliation":[{"name":"Centre for Liver and Gastrointestinal Research, Department of Immunology and Immunotherapy, College of Medicine and Health University of Birmingham  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kylie","family":"Savoye","sequence":"additional","affiliation":[{"name":"School of Mathematics, University of Birmingham  Birmingham 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