Deciphering the sympathetic nerve–fibroblast crosstalk in pancreatic cancer

Chronic stress–driven sympathetic signaling influences cancer development by reshaping the tumor microenvironment (TME). This dissertation reviews how sympathetic nerves regulate immune and stromal components across cancer types and focuses on their crosstalk with cancer‑associated fibroblasts (CAFs) in pancreatic ductal adenocarcinoma (PDAC). We show that sympathetic‑associated markers correlate with poor survival, and we introduce a pancreas‑specific sympathectomy model enabling long‑term denervation studies. Sympathetic signaling activates CAFs and remodels the TME, while CAFs heighten nerve injury responses, revealing reciprocal interactions that promote tumor progression. These findings identify a targetable neuro‑fibroblast axis and guide future investigation.