title: 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.
authors.affiliation: The Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: COk@mdanderson.org.
authors.forename: Chi Young
authors.initials: CY
authors.lastname: Ok
authors.affiliation: The Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: khyoung@mdanderson.org.
authors.forename: Ken H
authors.initials: KH
authors.lastname: Young
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D060890:B7-H1 Antigen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy* / Q000473:pathology*; D058990:Molecular Targeted Therapy / Q000379:methods*; D061027:Programmed Cell Death 1 Ligand 2 Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D061026:Programmed Cell Death 1 Receptor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D060890:B7-H1 Antigen; C423236:CD274 protein, human; C105992:PDCD1 protein, human; C556977:PDCD1LG2 protein, human; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor
keywords: Immune checkpoint; Lymphoid neoplasms; PD-1; PD-L1; PD-L2