Targeting the programmed death-1 pathway in lymphoid neoplasms

Abstract

Programmed death-1 (PD-1) is a co-inhibitory molecule and is seen in CD4+ and CD8+ T cells. Upon binding to its ligands, programmed death ligand-1 (PD-L1) and -2 (PD-L2), PD-1 negatively regulates interleukin 2 (IL-2) production and T cell proliferation. Activated effector T-cells, which kill cancer cells, can be affected by PD-1 signaling in some lymphoid neoplasm that express PD-L1 or PD-L2. PD-L1 expression in tumor cells can be induced by extrinsic signal (i.e. interferon gamma) or intrinsic signals, such as genetic aberrations involving 9p24.1, latent Epstein-Barr virus infection, PD-L1 3'- untranslated region disruptions, and activated Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. Anti-PD-1 therapy improves the overall response rate to treatment in patients with lymphoid neoplasms, particularly relapsed/refractory classical Hodgkin lymphoma. Inspired by their success in treating patients with classical Hodgkin lymphoma, medical practitioners have expanded PD-1 therapy, given as a single therapy or in combination with other drugs, to patients with other types of lymphoma. In this review, current clinical trials with anti-PD-1 or anti-PD-L1 drugs are summarized. The results of numerous clinical trials will broaden our understanding of PD-1 pathway and shall expand the list of patients who will get benefit from these agents including those who suffer from lymphoid neoplasms.

Keywords: Immune checkpoint; Lymphoid neoplasms; PD-1; PD-L1; PD-L2.