IL-22RA1/ STAT3 signaling promotes stemness and tumorigenicity in pancreatic cancer

Chronic inflammation is a feature of pancreatic cancer, but little is known about how immune cell or immune cell-related signal affects pancreatic cancer stemness and development. Our previous work showed that IL-22/IL-22RA1 plays a vital role in acute and chronic pancreatitis progression by mediating crosstalk between immune cells and acinar cells or stellate cells, respectively. Here we find IL-22RA1 is highly but heterogeneously expressed in pancreatic cancer cells, with high expression associated with poor prognosis of pancreatic cancer patients. The IL-22RA1hi population from pancreatic tumor harbored higher stemness potential and tumorigenicity. Notably, IL-22 promoted pancreatic cancer stemness via IL-22RA1/STAT3, which identified a functional signaling to regulate cancer stemness by microenvironmental factor. Moreover, STAT3 was indispensable for the maintenance of IL-22RA1hi cells. Overall, these findings provide a therapeutic strategy for PDAC patients with high expression of IL-22RA1.

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