Pulsed Electric Field Ablation versus Radiofrequency Thermal Ablation in Murine Breast Cancer Models: Anticancer Immune Stimulation, Tumor Response, and Abscopal Effects.

PURPOSE

To compare the immune response and survival after size-matched radiofrequency (RF) ablation 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, RF ablation, or PEF ablation. 4T1 tumor ablations included subgroups with intraperitoneal checkpoint inhibition immunotherapy (αPD-1). 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 cytokine profiling. Lungs were collected from 4T1-bearing mice for hematoxylin and eosin histology to assess metastatic spread and abscopal effect induced by ablation.

RESULTS

PEF elicited distinct immunomodulatory effects, with clear differences in serum and tumor cytokine profiles compared with RF ablation, including intratumoral downregulation of vascular endothelial growth factor, hypoxia-inducible factor 1α, c-MET, interleukin-10, Ki67, and tumor necrosis factor-α (all P < .05). PEF increased innate immune activation, with enhanced recruitment of dendritic cells, M1 macrophages, and natural killer cells coupled with a reduction in M2 macrophages and myeloid-derived suppressor cells (all P < .05). Concurrently, PEF strengthened adaptive immunity compared with RF ablation, characterized by increased antigen-specific T cells and decreased regulatory T cells (all P < .05). PEF stalled tumor growth and increased survival at the end of the study (≥4× versus RFA). Finally, PEF promoted an abscopal effect of clearing metastases in the lungs, which was stronger in combination with αPD-1 than with PEF alone.

CONCLUSIONS

The proprietary form of PEF used in this study evoked a preferential immunostimulatory profile versus RF ablation thermal ablation in mice, with implications for enhancing the therapeutic effectiveness of checkpoint inhibition immunotherapy for immunotherapy-unresponsive tumors.