Nano-Pulse Stimulation for the Treatment of Pancreatic Cancer and the Changes in Immune Profile

Abstract

A Pancreatic cancer is a notorious malignant neoplasm with an extremely poor prognosis. Current standard of care is rarely effective against late-stage pancreatic cancer. In this study, we assessed nanopulse stimulation (NPS) as a local treatment for pancreatic cancer in a syngeneic mouse Pan02 pancreatic cancer model and characterized corresponding changes in the immune profile. A single NPS treatment either achieved complete tumor regression or prolonged overall survival in animals with partial tumor regression. While this is very encouraging, we also explored if this local ablation effect could also result in immune stimulation, as was observed when NPS led to the induction of immune-mediated protection from a second tumor challenge in orthotopic mouse breast and rat liver cancer models. In the Pan02 model, there were insufficient abscopal effects (1/10) and vaccine-like protective effects (1/15) suggesting that NPS-induced immune mechanisms in this model were limited. To evaluate this further, the immune landscape was analyzed. The numbers of both T regulatory cells (Tregs) and myeloid derived suppressor cells (MDSCs) in blood were significantly reduced, but memory (CD44+) T-cells were absent. Furthermore, the numbers of Tregs and MDSCs did not reduce in spleens compared to tumor-bearing mice. Very few T-cells, but large numbers of MDSCs were present in the NPS treated tumor microenvironment (TME). The number of dendritic cells in the TME was increased and multiple activation markers were upregulated following NPS treatment. Overall, NPS treatments used here are effective for pancreatic tumor ablation, but require further optimization for induction of immunity or the need to include effective combinational NPS therapeutic strategy for pancreatic cancer.

Short-term observation of electric ablation with nanosecond pulsed electric field in the hepatic hilar area

“…The nanosecond pulsed electric field is an emerging locoregional electric ablative therapy that can be used to treat a variety of solid tumors, including melanoma [17], breast cancer [18], colon cancer [11], osteosarcoma [19], pancreatic cancer [20] and hepatocellular carcinoma [21]. The nonthermal characteristic and avoidance of heatsink effects are two of the most significant features of nsPEF ablation, which makes it possible to apply nsPEF ablation on liver tumors located near vital structures such as the porta hepatis.…”

Starting a Fire Without Flame: The Induction of Cell Death and Inflammation in Electroporation-Based Tumor Ablation Strategies

“…Recent in vivo findings provide greater mechanistic insight into the types of cell death induced by nsPEFs (118)(119)(120). Based on the inflammatory and immunomodulatory conditions, these studies reveal that nsPEFs may induce programmed necrosis or necroptotic cell death in breast, melanoma, and pancreatic cancers (118)(119)(120).…”

Patient Derived Xenografts Expand Human Primary Pancreatic Tumor Tissue Availability for ex vivo Irreversible Electroporation Testing

“…Several recent studies have revealed that IRE and other electroporation-based tumor ablation modalities significantly alters the tumor microenvironment and immune system activation (21,(24)(25)(26)(27)(28). In general, these studies show that irreversible electroporation results in a shift in the immunosuppressive tumor microenvironment to one that is more pro-inflammatory and anti-tumorigenic.…”