Pulsed Field Ablation Enables Stromal Manipulation and Tumor Reduction in Pancreatic Ductal Adenocarcinoma
- 1University of Nebraska Medical Center
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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BibTeX
@misc{demmel2026pulsed,
title = {{Pulsed Field Ablation Enables Stromal Manipulation and Tumor Reduction in Pancreatic Ductal Adenocarcinoma}},
author = {M. V. Demmel and L. N. Strickland and K. McAndrews and K. Turabi and A. Waller and S. Dash and U. K. Sardarni and N. Thosani and R. Viswanathan and J. M. Bailey-Lundberg},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.06.756887},
url = {https://www.biorxiv.org/content/10.64898/2026.10.06.756887v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Pulsed Field Ablation Enables Stromal Manipulation and Tumor Reduction in Pancreatic Ductal Adenocarcinoma
AU - M. V. Demmel
AU - L. N. Strickland
AU - K. McAndrews
AU - K. Turabi
AU - A. Waller
AU - S. Dash
AU - U. K. Sardarni
AU - N. Thosani
AU - R. Viswanathan
AU - J. M. Bailey-Lundberg
PY - 2026
DA - 2026/10/06
PB - bioRxiv
DO - 10.64898/2026.10.06.756887
UR - https://www.biorxiv.org/content/10.64898/2026.10.06.756887v1
AB - 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.
ER -