Irreversible electroporation combined with checkpoint blockade stimulates antitumor immune response in a hepatocellular carcinoma mouse model.

Abstract

Background: Irreversible electroporation (IRE) represents an innovative localized technique for tumor ablation, possessing the capacity to activate the immune response of the host. However, this method alone is inadequate to halt cancer progression, necessitating the integration of additional strategies to achieve effective immunotherapy.

Aim: To investigate the effects and underlying mechanisms of antitumor immunity derived from the synergistic application of IRE and anti-programmed cell death protein 1 (PD-1) therapy within a murine model of hepatocellular carcinoma.

Methods: C57BL-6 mice with tumor growth were divided into four separate cohorts: Control group; IRE group; Anti-PD-1 group; And IRE + anti-PD-1 group. The infiltration levels of T, B, and natural killer cells within the tumors, as well as the plasma concentrations of T helper type 1 cytokines (interleukin-2, interferon-γ, and tumor necrosis factor-β), were evaluated. Real-time polymerase chain reaction was utilized to quantify the expression of cluster of differentiation (CD) 8 (a marker indicative of CD8⁺ T cells) in the tumor specimens of the mice at various temporal intervals. Tumor growth trajectories were charted.

Results: The results indicated that the IRE + anti-PD-1 group exhibited significantly heightened percentages of T lymphocyte infiltration, particularly CD4⁺ and CD8⁺ T cells, when compared to the control cohort. Additionally, this group displayed increased infiltration of natural killer and B cells, augmented cytokine levels, and elevated CD8 messenger RNA expression. A marked decrease in tumor volume was noted in the IRE + anti-PD-1 group, indicating enhanced therapeutic efficacy.

Conclusion: The combined application of IRE and checkpoint blockade elicits an antitumor immune response, leading to a more substantial reduction in tumor volume and improved therapeutic outcomes, thereby establishing a novel avenue for the ablation and immunotherapy of hepatocellular carcinoma.