Immune and tissue response to Gene Electrotransfer in colon cancer using different electric pulses protocols

Gene electrotransfer (GET) has recently emerged as a promising non-viral approach for DNA delivery in gene therapy for several pathologies, including cancer. Multiple mechanisms have been identified that influence cell biology after exposure to reversible electroporation approaches, however the molecular effects of in vivo DNA delivery using different electrical pulse parameters are still poorly characterized.We focused on the transcriptomic profiling of murine colorectal tumors treated with two GET protocols for intratumoral delivery of plasmid DNA based on Short and High Voltage (SHV) electric pulses or on an adapted High Voltage - Low Voltage (HV-LV) pulses protocol. We also profiled by immunofluorescence the macrophages and T cells recruitment and we found a different intratumor macrophages infiltration between the treatments. Transcriptomic analysis revealed that, if apoptosis is a predominant mode of cell death due to the application of SHV pulses, the HV-LV protocol is associated with the activation of cell death signaling represented by the immunogenic necrotic pathways and with the activation of innate and adaptive immune response.These results suggest that specific pulse parameters can induce distinct immunomodulatory profiles in the tumor microenvironment that should be be considered for the selection of the most suitable GET-based approach for antitumor immunization.