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.
Show 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.
Matching journals
The top 9 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- Stromal architecture directs early dissemination in pancreatic ductal adenocarcinoma 91%
- Ddr1-Induced Neutrophil Extracellular Traps Drive Pancreatic Cancer Metastasis 91%
- Prebiotic proanthocyanidins inhibit bile reflux-induced esophageal adenocarcinoma through reshaping the gut microbiome and esophageal metabolome 91%
Similar papers in this journal
- Bringing the pancreas patient back to the bench: Ex vivo culture of intact human patient derived pancreatic tumour tissue 92%
- Intratumoral expression of IL-12 and CD40 ligand (CD154) from plasmids generates antitumor responses that eliminate tumoral T regs 92%
- Optogenetic Stimulation of Pancreatic Function via Vagal Cholinergic Axons 92%
Similar papers in this journal
Similar papers in this journal
- Immune stromal components impede biological effectiveness of carbon ion therapy in a preclinical model of pancreatic ductal adenocarcinoma 92%
- Immunomodulation of Pancreatic Cancer via Inhibition of SUMOylation and CD155/TIGIT Pathway 92%
- Early assessment of molecular progression and response by whole-genome circulating tumor DNA in advanced solid tumors 90%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.