Effects of Irreversible Electroporation on the Tumor Microenvironment in Pancreatic Ductal Adenocarcinoma: A Narrative Review

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, largely due to late diagnosis, aggressive tumor biology, and marked resistance to conventional treatment and immunotherapy. A major contributor to therapeutic failure is the highly immunosuppressive and desmoplastic tumor microenvironment (TME), which limits drug delivery, restricts cytotoxic immune-cell infiltration, and promotes immune evasion. This narrative literature review evaluates the effects of irreversible electroporation (IRE) on the PDAC microenvironment and assesses its potential role as an immune-sensitizing strategy capable of enhancing antitumor immunity and improving responsiveness to immunotherapy. English-language review articles, preclinical and clinical studies published between 2011 and 2025, were investigated, with a particular focus on evidence from 2020 to 2025. The reviewed literature suggests that IRE can induce immunogenic cell death by releasing danger-associated molecular patterns, enhance antigen presentation, remodel the fibrotic stroma, reduce hypoxia, and promote infiltration of cytotoxic T lymphocytes. Several studies also report reductions in immunosuppressive cell populations and improved responses to immune checkpoint blockade following IRE. Overall, IRE appears to be a promising local treatment modality with systemic immunomodulatory potential in PDAC. However, most evidence remains preclinical, and further prospective clinical studies are required to define its long-term efficacy, safety profile, optimal technical parameters, and best integration with systemic immunotherapy.