Activin a promotes progression of pancreatitis into pancreatic cancer

The five-year survival rate for pancreatic cancer patients remains at 13%. Acute pancreatitis and chronic pancreatitis are risk factors for developing pancreatic cancer, suggesting a strong inflammatory role for disease initiation. Recently, we found that activin a (activin), a TGFβ superfamily member, drives inflammation in acute pancreatitis via recruitment of macrophages and activation of neutrophils. Here, we expand our studies in pancreatic cancer in the setting of inflammation and activin signaling. We performed digital spatial profiling (DSP) on a tissue section of human chronic pancreatitis with suspicion of pancreatic cancer to quantify more than 50 proteins relative to activin expression in situ. We found that activin co-localization is associated with reduced T cell activation and increased MAPK and PI3K signaling. These data suggest a previously underappreciated immunomodulatory role for activin in the setting of pancreatic cancer.