Pulsed Field Ablation Enables Stromal Manipulation and Tumor Reduction in Pancreatic Ductal Adenocarcinoma

Demmel, M. V.; Strickland, L. N.; McAndrews, K.; Turabi, K.; Waller, A.; Dash, S.; Sardarni, U. K.; Thosani, N.; Viswanathan, R.; Bailey-Lundberg, J. M.

doi:10.64898/2026.10.06.756887

bioRxiv · 10.64898/2026.10.06.756887

Pulsed Field Ablation Enables Stromal Manipulation and Tumor Reduction in Pancreatic Ductal Adenocarcinoma

Demmel, M. V.·Strickland, L. N.·McAndrews, K.·Turabi, K.·Waller, A.·Dash, S.·Sardarni, U. K.·Thosani, N.·Viswanathan, R.·Bailey-Lundberg, J. M.

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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 SMA-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-{beta} response signatures. Serial PFA treatments further suppressed EMT-associated programs, identifying stromal reprogramming as a potential mechanism through which PFA enhances tumor control.

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Demmel, M. V., Strickland, L. N., McAndrews, K., Turabi, K., Waller, A., Dash, S., Sardarni, U. K., Thosani, N., Viswanathan, R., Bailey-Lundberg, J. M.. 2026-10-07. Pulsed Field Ablation Enables Stromal Manipulation and Tumor Reduction in Pancreatic Ductal Adenocarcinoma. https://doi.org/10.64898/2026.10.06.756887

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