ArticleJHEP reports : innovation in hepatology2026
Elevation of liver elasticity following radiofrequency ablation reflects neutrophil-mediated abscopal effect in liver cancer.
Article in JHEP reports : innovation in hepatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
BACKGROUND &
aimsHepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality globally. Radiofrequency ablation (RFA) is a widely used treatment for HCC, but its efficacy is often limited by tumor relapse. Neutrophils, which serve as a double-edged sword in tumor immunology, have recently been implicated in antitumor immunity post RFA. Shear wave elastography (SWE) is a non-invasive examination of liver tissue and is associated with immune response. This study investigates the correlation between dynamic changes in SWE values and neutrophil response following RFA, and explores potential adjuvant strategies for RFA.
methodsWe conducted a comprehensive analysis using both clinical data from patients undergoing RFA (n = 102) and experimental studies in mouse models (n = 4-6 per group). Single-cell RNA sequencing (scRNA-seq) and multi-omics analyses, including multiplex immunofluorescence staining and flow cytometric analysis, were performed to identify neutrophil subsets. To assess the therapeutic potential of neutrophil-activating therapy to enhance antitumor immunity post RFA, we tested a CD40 agonist in combination with RFA in preclinical models.
resultsIncreasing liver SWE values following RFA were significantly associated with reduced relapse (n = 102, p <0.001), a phenomenon that was linked to the inflammatory environment induced by the infiltration of neutrophils (2.5-fold increase, p <0.001). scRNA-seq analysis identified neutrophil subsets characterized by high expression of IFN-stimulated genes, which exhibited potent antitumor activity via nitric oxide. Importantly, treatment with a CD40 agonist significantly augmented this immune response, leading to reduced tumor growth in mice (149.6 ± 38.12 mm
conclusionsOur results linked clinical features to neutrophil-mediated immunity post RFA. Thus, neutrophil-activating therapies, such as CD40 agonists, could prevent HCC relapse after RFA. IMPACT AND IMPLICATIONS: We report that increases in liver SWE are linked with neutrophil infiltration, providing a non-invasive biomarker for monitoring HCC relapse post RFA. Thus, pioneering innate immune modulators, such as CD40 agonists, could be viable adjuvant strategies following RFA.
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