Targeting the programmed death-1/programmed death-ligand 1 axis in lymphoma.

The development of 'immune checkpoint inhibitors' or drugs targeting the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) axis has been a stunning success of cancer immunotherapy. This review provides a timely overview of the biology and function of the PD-1 pathway and discusses the rationale for therapeutic inhibition of this pathway in lymphoma. Recent studies have evaluated the prevalence and prognostic implications of PD-1, PD-L1/2 expression in various lymphoma subtypes. We present an overview of the clinical trials evaluating pidilizumab, nivolumab, and pembrolizumab in patients with lymphoid malignancies, and highlight some of the more promising agents in this class, currently in development. Finally, we discuss biomarkers that may predict response to therapy in patients with lymphoma across these clinical trials. A plethora of clinical trials are in progress testing immune checkpoint inhibitors in many subtypes of lymphoma, which will define their role both as a monotherapy and in combination with other biologic agents.