Contemporary clinical trials in pancreatic cancer immunotherapy targeting PD-1 and PD-L1

Abstract

Pancreatic cancer (PC) is a major gastrointestinal cancer in terms of worldwide incidence and mortality. Despite advances in diagnostic and treatment modalities, the mortality of PC is still a serious concern in both sexes. Immune therapy using inhibitors of immune checkpoints, especially inhibitors of programmed cell death protein 1/programmed cell death ligand-1(PD-1/PD-L1), offer huge benefits to cancer patients. This review describes an up-to-date information on the role of PD-1 and PD-L1 in the development of immune tolerance in PC alongside the current clinical trials and the known outcomes citing the available literature. We also included the details on PD-1/PD-L1-mediated signalling in maintenance of PC stem cells and metastasis. We reviewed the critical information on safety, tolerance, and efficacy of clinically important regimens of PD-1/PD-L1 blocking agents and targeted therapeutics. This review elucidates the underlying mechanisms of PD-1/PD-L1 alliance in tolerance of the immune system, maintenance of stem cells, and metastasis promotion as well as design regimens with high safety and excellent tolerability and efficacy for management of PC in advanced stages.

Keywords: Immune checkpoints; Immune therapy; Metastasis; Pancreatic cancer.