{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T02:38:23Z","timestamp":1790563103700,"version":"4.1.0"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"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":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Liver ablation or resection can cure early-stage hepatocellular carcinoma (HCC), yet late diagnosis and high relapse rates hinder long-term survival. We sought to delineate how tumor burden\u2014and its removal\u2014reshape the systemic immune transcriptome and extract blood-based signatures with diagnostic and prognostic potential.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>Peripheral blood mononuclear cells (PBMCs) from six early-stage HCC patients were subjected to single-cell RNA sequencing (scRNA-seq) both prior to and 1\u20133 months following curative therapy, alongside six age-matched healthy controls. The data were integrated with independent bulk PBMC transcriptomes and public single-cell datasets of paired tumor and adjacent liver immune cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>\n                      Pre-therapy PBMCs displayed an immunosuppressive transcriptional program characterized by elevated TGF beta signaling and ubiquitin-mediated proteolysis. Curative therapy attenuated these pathways and partially restored interferon responses, cytotoxic gene expression, and intercellular communication, although the values remained below healthy levels. We cross-validated these features in tissue, identifying concordant immunosuppressive signatures in tumor versus adjacent-liver immune cells. An immunosuppressive CD14\n                      <jats:sup>+<\/jats:sup>\n                      monocyte subset that expands in the blood of HCC patients displays a transcriptional program matching an IL-10\u2013rich, M2-like macrophage population in liver tissue. A 23-gene signature from this subset was significantly up-regulated in bulk PBMCs from HCC patients (diagnostic) and associated with poor overall survival in the TCGA-LIHC cohort (prognostic). Among these genes, ABCA1 marked monocytes and macrophages with high TGF beta signaling, accurately reflecting tumor-associated immunosuppression in blood and liver.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Early-stage HCC induces a reversible, systemic immunosuppressive transcriptome captured by a monocyte-derived 23-gene blood signature; tumor removal partially restores this profile within three months. These results highlight the potential of blood-derived monocyte signatures as noninvasive biomarkers of HCC-associated immunosuppression and clinical outcome.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1717978","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T05:35:01Z","timestamp":1768973701000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["A monocyte-derived blood transcriptomic signature reveals systemic immunosuppression in HCC and partial reversal following curative therapy"],"prefix":"10.3389","volume":"16","author":[{"given":"Liang","family":"Zhou","sequence":"first","affiliation":[{"name":"Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH)","place":["Hannover, Germany"]},{"name":"TWINCORE, Centre for Experimental and Clinical 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