Irreversible Electroporation has More Synergistic Effect with Anti-PD-1 Immunotherapy than Thermal Ablation or Cryoablation, in a Colorectal Cancer Model

Abstract

Boosting the response rate of immune checkpoint blockade (ICB) therapy to improve treatment efficacy is a primary goal in cancer immunotherapy. One of the promising approaches involves focal tumor ablation to reduce tumor burden and trigger the in situ vaccination. Even though this combination strategy has demonstrated enhanced therapeutic outcomes in both preclinical research and clinical trials, limited research has comparatively investigated diverse ablation techniques. The optimal choice among focal therapy techniques remains largely unknown. In a murine colorectal cancer model (MC-38), the therapeutic efficacy of anti-PD-1 in combination with thermal ablation, cryoablation, and irreversible electroporation (IRE) is evaluated, utilizing well-characterized miniature probes. In this model, ICB monotherapy has limited effect in controlling tumor growth. IRE exhibits the most favorable synergistic effect with anti-PD-1 immunotherapy than thermal ablation or cryoablation, leading to the greatest primary tumor growth delay, longest tumor-free survival, and highest protection against secondary tumor challenge. Furthermore, the co-administration of IRE and anti-PD-1 significantly fosters the infiltration of CD8+ T cells into the tumor coupled with a remarkable stem-like progenitor phenotype. The findings demonstrate that IRE stands as a promising modality that can potentiate the antitumor efficacy when the tumor is poorly responding to ICB monotherapy.