USP22 and familial pancreatic carcinoma: Other inflammatory mediators secreted by PDA cells include granulocyte colony-stimulating factor (G-CSF) (41), IL-6 (42), IL-1α (43), IL-1β (44, 45), ubiquitin specific peptidase 22 (USP22) (46), C-X-C motif chemokine ligand 8 (CXCL8) (47), matrix metallopeptidase 9 (MMP-9) and indoleamine-2,3-dioxygenase (IDO) (48), which all contribute to the establishment of immunosuppressive TME in pancreatic cancer (Figure 1).