Immunological effect of irreversible electroporation on hepatocellular carcinoma

Abstract

Background: This study intends to investigate the immunological effects of tumor ablation with irreversible electroporation (IRE). Methods: We evaluated the systemic immune response in patients with hepatocellular carcinoma (HCC) after IRE treatment. Furthermore, we analyzed the tumor infiltrating T lymphocytes and the level of serum cytokines in IRE and control groups of tumor-bearing mice. Results: We observed that IRE induced an increase in WBC, neutrophil and monocyte counts and a decrease in lymphocyte count 1 day post-IRE and returned to baseline values within 7 days in the patients. Meanwhile, circulating CD4+ T cell subsets, but not CD8+, decreased 1 day post-IRE. The activated T cells and natural killer (NK) cells increased, and regulatory T (Treg) cells decreased. Furthermore, a significant increase in cytotoxic CD8+ T cells infiltration was observed on ablative tumors in mice. The level of serum IFN-γ also significantly increased in the IRE group. Conclusions: Our study demonstrated that IRE upregulated activated T cells and downregulated Tregs in the peripheral blood of patients. Meanwhile, the results from the animal model indicated that IRE could induce antitumor adaptive immunity dominated by the infiltration of cytotoxic CD8+ T cells into the tumors, accompanied by reduced Tregs.