More Ultrasound-Guided Percutaneous Microwave Ablation Leads to Higher Immune-Related Gene Expression and Boosts PD-1 Monoclonal Antibodies for Liver Cancer

Abstract

The aim of the work described here was to investigate the relative contribution of subtotal ultrasound-guided percutaneous microwave ablation (MWA) to amplifying programmed cell death protein-1 (PD-1) inhibition in advanced hepatocellular carcinoma (HCC). Between April 2019 and December 2021, advanced HCC patient demographics, tumor response, survival data, neutrophil-to-lymphocyte ratio (NLR) and peripheral lymphocyte profiles were retrospectively collected and analyzed. In hepa1-6 tumor-bearing C57BL/6J mice, RNA sequencing, flow cytometry, immunohistochemistry staining and cytokine tests were also performed. Twenty-nine HCC patients were enrolled, with a median follow-up duration of 15.1 mo. Compared with the ablation rate (AR) ≤50% group (n=10), the AR >50% group (n=19) had a higher disease control rate, a longer time to progression and a longer overall survival. More patients in the AR >50% group had an early decrease in NLR and better immune activation. RNA sequencing of murine tumors subjected to MWA >50% AR showed that immune-related gene expression upregulated. CD8+ T cells, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) were also increased, indicating that MWA >50% AR boosted the immunomodulatory effect of PD-1 inhibitors. More MWA could induce superior antitumor immunity by enhancing immune-related gene expression, priming CD8+ T cells and thereby boosting PD-1 inhibition. It is advisable that eradication of tumors to the degree possible should be considered within technical access to obtain a better prognosis.