Immunomodulatory Effect after Irreversible Electroporation in Patients with Locally Advanced Pancreatic Cancer

He, Chaobin; Wang, Jun; Sun, Shuxin; Zhang, Yu; Li, Shengping

Pancreatic adenocarcinoma is a lethal disease with extremely poor prognosis, which also represented the seventh and sixth leading causes of cancer-related death in the world and in China, respectively. The 5-year survival rate is only 5% [1, 2] . Surgical resection is the only chance to obtain curative treatment while it is only suitable for less than 20% of patients with this disease [3] . Approximately 40% of new cases are diagnosed with locally advanced pancreatic cancer (LAPC), which is characterized by the involvement of major vascular structures, such as celiac trunk, superior mesenteric artery, leading to unresectable but nonmetastatic diseases [4] . Currently, the treatment for LAPC remains a huge challenge due to the poor prognoses of this disease. Limited responses and little impact on survival or life were achieved after the standard treatments, which was mainly systemic chemotherapy [5, 6] . Moreover, the high rates of adverse events due to the toxicity of chemotherapy limited the use and promotion of treatment, such as the combination chemotherapy of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX), even though it was shown to display some progression in improving the survival of patients with LAPC [7] [8] [9] . Therefore, it is necessary to evaluate new treatment to optimize common therapeutic approaches. Nowadays, local therapies were shown to improve the prognosis of LAPC patients with varying degrees of success [10] . 2 Journal of Oncology Irreversible electroporation (IRE), a nonthermal ablation technique, is established as a local ablative therapy for patients with LAPC with promising outcomes of increasing overall survival (OS) from 12 months to 25 months [11] . It is a novel local destructive method based on the transmission of high voltage currents through the tumor via needles, leading to cell membrane defects and apoptotic death [12, 13] . Additionally, during the induction process of apoptotic death by IRE, the structure and composition of the tumor microenvironment are changed, inducing an intense inflammatory cell response, which is characterized by the infiltration of immune cells [14] . It was shown that this IRE-induced immunomodulatory was not only limited to the ablated areas, but also a systemic reaction [15] . Thus, IRE could be regarded as a potential immunomodulatory treatment and might induce extensive changes of immune cells or indexes after ablation.