VSIR and familial pancreatic carcinoma: Mechanistically, TLR4 enhanced the expression of the immune checkpoint molecules such as programmed death ligand-1 (PD-L1) [37] and V-domain Ig suppressor of T cell activation (VISTA) [38] in pancreatic cancer cells, as well as upregulated the production of anti-inflammatory IL-35 from regulatory B cells [39], all of which promoted the formation of an immunosuppressive microenvironment in pancreatic cancer.