Pulsed Electric Field (PEF) Ablation Invokes Stronger Immune Cytokine Profile and Tumor Response than Radiofrequency Thermal Ablation for Matched Ablation Volumes

Focal tumor ablation may cause secondary immunogenic upregulation that enhances local and distant tumor responses, with profiles that are unique to each modality.,

Pulsed electric fields (PEFs) use short duration-high voltage electrical pulses to destabilize and kill cells through various biochemical processes. Because it does not rely on thermal effects PEF does not damage interstitial proteins, fostering improved antigen integrity and immune signaling which may lead to lesion resolution.
This study compared whether cell death and subsequent interstitial effects caused by PEF and radiofrequency ablation (RFA) result in differentiated primary tumor responses.

Materials and Methods:

Thirty female Balb/c mice, divided into Sham, PEF, and RFA treatment groups (n=10/group) were transplanted with EMT6 cells in the left mammary fat pad. Eight days after challenge (d=0), mice in the PEF and RFA groups received treatment with doses selected to achieve similar subtotal ablation volumes. Three mice from each group were euthanized at day 4 for H&E analysis of ablation zone. The remainder were survived to 10-days post-ablation to monitor tumor growth. Serum was collected on Days -1, +1, +4 and +10 for cytokine analysis.

Results:

Four-day histology demonstrated comparable subtotal ablation areas between PEF and RFA treatment. While RFA-treated tumors presented immune cells accumulating at the tumor-treatment zone boundary, PEF-treated tumors showed immune cell infiltration throughout the tumor. Further, PEF treatment slowed tumor growth compared to RFA or Sham treatments, with day 10 average tumor volumes of 335, 791, and 857 mm³ for PEF, RFA, and sham group, respectively.

Ingenuity Pathway Analysis (IPA) of 32 serum cytokines revealed most notable differences between groups on day 4 post-ablation. The PEF-treated group had a significant decrease in the levels of CSF1, CSF2, CSF3, CCL2, IL1β, IL6, IL13, and TNF, and an increase in the levels of IL4. These changes suggest that PEF is associated to 1) decreased accumulation of myeloid derived suppressor cells (MDSCs), 2) decreased the proliferation of tumor-associated macrophages (TAMs), 3) decreased proliferation, survival and invasion of tumor cells. Conversely, these changes were all the opposite for the RFA group.

Conclusion:

PEF treatment may cause a stronger EMT6 tumor response in mice compared to RFA treatment. These data suggest that PEF may have a greater local and distant tumor response benefit versus RFA thermal ablation. Further studies should explore potential abscopal effects.