Abstract
Nanosecond pulsed electric fields (nsPEFs) have emerged as a novel and effective strategy for the non-surgical and minimally invasive removal of tumors. However, the effects of nsPEFs treatment on the tumor immune microenvironment remain unknown. In this study, the changes in the morphology and function of pancreatic cancer cells after nsPEFs were assessed and the modifications in the immune profile in pancreatic cancer models were investigated. To this end, electrodes were inserted with different parameters applied to ablate the targeted tumor tissues. Tumor development was found to be inhibited, with decreased volumes post-nsPEFs treatment compared with control tumors (P < 0.05). Hematoxylin and eosin staining showed morphological changes in pancreatic cancer cells, Ki-67 staining confirmed the effects of nsPEFs on tumor growth, and caspase-3 staining indicated that nsPEFs caused apoptosis in the early stages after treatment. Three days after nsPEFs, positron emission tomography demonstrated little residual metabolic activity compared with the control group. Gene expression profiling identified significant changes in immune-related pathways. After treatment with nsPEFs, CD8+ T lymphocytes increased. We showed that nsPEFs led to a significant decrease in immune suppressive cells, including myeloid derived suppressor cells, T regulatory cells, and tumor-associated macrophages. In addition, the levels of TNF-α and IL-1β increased (P < 0.05), while the level of IL-6 was decreased (P < 0.05). NsPEFs alleviated the immunosuppressive components in pancreatic cancer stroma, including hyaluronic acid and fibroblast activation protein-α. Our data demonstrate that tumor growth can be effectively inhibited by nsPEFs in vivo. NsPEFs significantly altered the infiltration of immune cells and triggered immune response.
Highlights
Pancreatic cancer is one of the most virulent malignancies, with a rapid progression, a low rate of resectability, and an extremely poor prognosis
patient-derived tumor xenograft (PDX) models provide additional material to examine the biology of pancreatic cancer, and serve as a robust and preclinical model to examine the efficacy of this potential new therapy
Our results showed that the differences in dose effect for Nanosecond pulsed electric fields (nsPEFs) and the number of pulses and voltage are all significant factors that influence the effect of this treatment
Summary
Pancreatic cancer is one of the most virulent malignancies, with a rapid progression, a low rate of resectability, and an extremely poor prognosis. It is estimated that the 5-year overall survival rate for patients with pancreatic cancer is only about 3% [1]. 15–20% of patients have the chance of surgical resection at the beginning of diagnosis, but only 20% of these survive for 5 years [2]. The recommended treatment for unresectable pancreatic cancer is systemic chemotherapy or combined radiotherapy, the median overall survival remains poor (6–12 months) [3]. Current guidelines do not recommend surgery for patients with metastatic pancreatic cancer. Local ablative strategies such as radiofrequency ablation, irreversible electroporation (IRE), and stereotactic body radiation have already gained their place as options to achieve disease control and long-term survival in addition to standard chemotherapy [4]
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