Irreversible electroporation combined with anti-programmed cell death protein 1 therapy promotes tumor antigen-specific CD8+ T cell response.

Abstract

Background: Irreversible electroporation (IRE) is a novel local tumor ablation approach with the potential to activate the host's immune system. However, this approach is insufficient to prevent cancer progression, and complementary approaches are required for effective immunotherapy.

Aim: To assess the immunomodulatory effects and mechanism of IRE combined anti-programmed cell death protein 1 (PD-1) treatment in subcutaneous pancreatic cancer models.

Methods: C57BL-6 tumor-bearing mice were randomly divided into four groups: Control group; IRE group; anti-PD-1 group; and IRE + anti-PD-1 group. Tumor-infiltrating T, B, and natural killer cell levels and plasma concentrations of T helper type 1 cytokines (interleukin-2, interferon-γ, and tumor necrosis factor-α) were evaluated. Real-time PCR was used to determine the expression of CD8 (marker of CD8⁺ T cells) in tumor tissues of the mice of all groups at different points of time. The growth curves of tumors were drawn.

Results: The results demonstrated that the IRE + anti-PD-1 group exhibited significantly higher percentages of T lymphocyte infiltration, including CD4⁺ and CD8⁺ T cells compared with the control group. Additionally, the IRE + anti-PD-1 group showed increased infiltration of natural killer and B cells, elevated cytokine levels, and higher CD8 mRNA expression. Tumor volume was significantly reduced in the IRE + anti-PD-1 group, indicating a more pronounced therapeutic effect.

Conclusion: The combination of IRE and anti-PD-1 therapy promotes CD8⁺ T cell immunity responses, leading to a more effective reduction in tumor volume and improved therapeutic outcomes, which provides a new direction for ablation and immunotherapy of pancreatic cancer.