Epigenetic regulation of PD-L1 expression and pancreatic cancer response to checkpoint immunotherapy

Checkpoint blockade cancer immunotherapy, including anti-PD-1 and anti-PD-L1 antibody immunotherapy, has shown durable efficacy in many types of human cancers. However, pancreatic cancer is one of the few cancers that do not respond to anti-PD-1/PD-L1 immunotherapy (1). It has been shown that targeted therapy can increase the efficacy of checkpoint immunotherapy against pancreatic cancer (2,3), but the mechanisms underlying this non-response of pancreatic cancer is still unknown. In a recent study, we showed that PD-L1 is uniformly and abundantly expressed on the surface of 9 of the 10 human pancreatic cancer cell lines obtained from American Type Culture Collection (Manassas, VA, USA). Using a FDA-approved PD-L1-specific antibody, we also detected abundant membrane and cytoplasmic PD-L1 expression in human pancreatic cancer specimens.