Ke Lin, Jiayao Huang, Nan Zhang, Bin Qiao, Daopeng Yang, Jianping Guo, Xiaoyan Xie, Manxia Lin, Bowen Zhuang
BACKGROUND & AIMS: Hepatocellular 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. METHODS: We 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. RESULTS: , p = 0.008). CONCLUSIONS: Our 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.