Pulsed Electric Field (PEF) Ablation versus Radiofrequency Thermal Ablation in Murine Breast Cancer Models: Anti-Cancer Immune Stimulation, Tumor Response, and Abscopal Effects

PURPOSE This study compares the immune response and survival following size-matched Radiofrequency (RFA) and a proprietary form of Pulsed Electric Field (PEF) ablation in murine tumors. MATERIAL AND METHODS Orthotopically inoculated EMT6 or 4T1 murine tumors received Sham, RFA, or PEF ablation. 4T1 tumor ablations included subgroups with checkpoint inhibition immunotherapy (αPD-1) administered intraperitoneally. Blood was collected for cytokine profiling and flow cytometry. Tumor size was measured and survival was monitored. Tumor samples were processed for histology, immunohistochemistry, flow cytometry, and cytokines profiling. Lungs were collected in 4T1-bearing mice for H&E histology to check metastatic spread and abscopal effect evoked by ablation. RESULTS PEF elicited distinct immunomodulatory effects, with stark differences in serum and tumor cytokine profiles compared to RFA, including intratumoral downregulation of VEGF, HIF1α, c-MET, IL-10, Ki67, and TNFα (all p<0.05). PEF increased innate immune activation, with enhanced recruitment of Dendritic Cells, M1 macrophage, and Natural Killer cells; coupled with a reduction in M2 macrophages and Myeloid-Derived Suppressor Cells (all p<0.05). Concurrently, PEF strengthened adaptive immunity compared to RFA, characterized by increased antigen-specific T-cells and decreased T-regulatory cells (all p<0.05). Finally, PEF stalled tumor growth and increased survival to the end of the study (≥4x). PEF promoted an abscopal effect clearing metastases in the lungs, which was stronger when combined with αPD-1 than PEF-alone. CONCLUSION The proprietary form of PEF used here evokes a preferential immunostimulatory profile versus RFA thermal ablation, with implications for enhancing therapeutic efficacy of checkpoint inhibition immunotherapy for immunotherapy-unresponsive tumors in mice.