Peri-interventional neutrophil extracellular traps and immune surveillance in hepatocellular carcinoma: mechanisms, biomarkers, and recurrence after liver resection or thermal ablation.

Authors

Hang Xu, Jiayang Yi, Wanwan Zhang, Shaojie Zhu, Zhigang Liu

Published in

Frontiers in oncology. Volume 16. Pages 1988923. Epub Sep 28, 2026.

Abstract

Recurrence remains common after curative-intent liver resection or thermal ablation for hepatocellular carcinoma (HCC). These interventions transiently remodel the hepatic and treatment-bed immune microenvironment through overlapping but distinct processes, including tissue injury, vascular and coagulation activation, neutrophil recruitment, and, particularly during resection, hepatic ischemia-reperfusion. We organize the evidence using a peri-interventional two-component heuristic: chronic liver disease and tumor-associated inflammation may shape baseline susceptibility, whereas acute treatment injury may trigger intervention-specific neutrophil extracellular trap (NET) accumulation. Experimental studies across liver-intervention and cross-cancer models link NETs to impaired CD8⁺ T-cell immunity, tumor-cell retention, extracellular-matrix remodeling, and metabolic adaptation. Patient-linked evidence remains limited and largely associative; much of the mechanistic framework therefore relies on colorectal liver metastasis and cross-cancer models. Translational studies should distinguish monitoring, pharmacodynamic, prognostic, and predictive applications and prioritize serial MPO-DNA as the best-supported circulating peri-interventional candidate, with NE-DNA or H3Cit-based measures as supportive assays and spatial validation where feasible. Candidate preclinical approaches include limiting NET formation, degrading established NET structures, and disrupting NET-target-cell signaling. NET-checkpoint combinations remain preclinical hypotheses, particularly because current phase III adjuvant ICI studies have not established postoperative HCC benefit. Because NET and neutrophil functions are context dependent, prospective studies should define intervention-specific NET kinetics, immune correlates, target engagement, recurrence phenotype, and safety.

PMID:
42865793
Bibliographic data and abstract were imported from PubMed on 13 Oct 2026.

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