Pulsed Field Ablation Enables Stromal Manipulation and Tumor Reduction in Pancreatic Ductal Adenocarcinoma
Year: 2026
Type: preprint
Abstract: ABSTRACT Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense desmoplastic microenvironment that promotes therapeutic resistance and disease progression. Here, we investigated the impact of pulsed field ablation (PFA), a non-thermal electroporation-based therapy, on tumor and stromal remodeling in a syngeneic murine PDAC model. PFA induced rapid apoptotic and necrotic tumor cell death, transient neutrophil infiltration, and durable suppression of tumor growth. Single-cell RNA sequencing following repeated PFA treatments revealed enrichment of a classical secretory tumor cell state associated with complement and stress-response pathways and reduced epithelial-to-mesenchymal transition (EMT) programs. Although overall immune composition was largely unchanged, PFA markedly remodeled the stromal compartment, decreasing αSMA-positive activation and shifting cancer-associated fibroblasts (CAFs) from tumor-promoting myofibroblastic CAFs toward Dpp4 + complement-secreting CAFs. This transition was accompanied by increased IL-1 signaling potential, reduced Tgfb1 expression, and diminished tumor cell TGF-β response signatures. Serial PFA treatments further suppressed EMT-associated programs, identifying stromal reprogramming as a potential mechanism through which PFA enhances tumor control. Statement of Significance PFA suppresses PDAC growth while reprogramming the tumor stroma. PFA shifts CAFs from myofibroblastic to Dpp4+ complement-secreting states, reduces TGF-β and EMT signaling, and promotes durable tumor control through stromal remodeling.
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7220834171