Abstract
BackgroundThis study intends to investigate the immunological effects of tumor ablation with irreversible electroporation (IRE).MethodsWe 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.ResultsWe 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.ConclusionsOur 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.
Highlights
This study intends to investigate the immunological effects of tumor ablation with irreversible electroporation (IRE)
An immediate innate immune response was observed after IRE Peripheral blood samples obtained from 11 patients with hepatocellular carcinoma (HCC) at six different time points, pre- and post-IRE
IRE led to a slight and nonsignificant increase on the percentage of natural killer (NK) cells (CD56+CD16+) on day 1 (11.4 ± 8.5 vs 15.9 ± 9.7%), followed by a decrease on day 3, a significant increase was observed from day 3 to day 14 (10.4 ± 6.4 vs 15.3 ± 8.2%, p < 0.05) (Fig. 1f)
Summary
This study intends to investigate the immunological effects of tumor ablation with irreversible electroporation (IRE). Image-guided tumor ablation therapies such as radiofrequency ablation, microwave ablation and cryoablation are in widespread clinical use to treat a broad range of benign or malignant solid tumors [1, 2]. Its efficacy is not impaired by heat sink effects in the treatment of tumors located close to large blood vessels [5, 6]. These advantages make IRE suitable to target tumors that cannot be treated by thermal ablations. The literature on immune cell recruitment after IRE treatment remain conflicting, there is strong evidence of local and systemic antitumor immune response resulting from IRE
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