Hypoxic cancer-associated fibroblast (CAFs) in pancreatic ductal adenocarcinoma (PDAC) of mice significantly promoted M2 polarization of TAMs in an HIF-2α-dependent manner in the PDAC, indicating that HIF-2α in CAFs plays a crucial role in hypoxia-related immunosuppression and tumor growth in pancreatic cancer [46]. This evidence concerns the gene EPAS1 and familial pancreatic carcinoma.