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NFAT Mediates Pro-Tumorigenic Inflammation in Cancer-Associated Fibroblasts in Pancreatic Ductal Adenocarcinoma [mouse multiome]

GSE292094 Mus musculus Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing 8 samples Submitted 2025/12/08 Platform GPL24247
Summary
Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense stroma, low immunogenicity, and resistance to therapy. Cancer-associated fibroblasts (CAFs) are key stromal cells within the tumor microenvironment (TME) that drive tumor progression. Interleukin-1 (IL-1) promotes fibrosis, pathogenic inflammation, and poor prognosis in PDAC. Using a novel single-cell multiomic approach, we investigate the IL-1 signaling axis in human and mouse models of PDAC, identifying nuclear factor of activated T cells (NFAT) transcription factors as key mediators. IL1R1+ CAFs activate an inflammatory phenotype associated with elevated NFAT motif activity and gene expression. In vivo, NFAT inhibition in a mouse model of PDAC significantly reduces tumor weight and fibrosis, supporting its pro-tumorigenic role. Our findings suggest that NFAT mediates IL-1-induced inflammation in PDAC, highlighting its potential as a therapeutic target. This study demonstrates the power of multiomic analyses to uncover therapeutic targets within the complex tumor microenvironment.
Published in
NFAT mediates pro-tumorigenic inflammation in cancer-associated fibroblasts in pancreatic ductal adenocarcinoma
Guo C, Griffin MF, Morgan AG et al. · Cell reports 2026 · PMID 41533513 · doi:10.1016/j.celrep.2025.116849
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Also filed as BioProject PRJNA1236853 and SRA study SRP570781. Searching any of these in the dataset finder brings you back here.

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