Manipulating the PD-1 pathway to improve immunity

• Type of Material: Article
• Authors: Alice O Kamphorst Silva, Emory University; Rafi Ahmed, Emory University
• Language: English
• Date: 2013-06-01
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 Elsevier Ltd. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1016/j.coi.2013.03.003
• Title of Journal or Parent Work: Current Opinion in Immunology
• ISSN: 0952-7915
• Volume: 25
• Issue: 3
• Start Page: 381
• End Page: 388
• Grant/Funding Information: This work was supported by grants from the National Institutes of Health R01 AI030048 and P01 A1080192 (RA) and by the Irvington Institute Fellowship Program of the Cancer Research Institute (AOK).
• Keywords: Science & Technology; NEGATIVE REGULATOR; Life Sciences & Biomedicine; CHRONIC VIRAL-INFECTION; IN-VIVO; EXPRESS HIGH-LEVELS; T-CELL EXHAUSTION; INHIBITORY RECEPTOR PD-1; MELANOMA PATIENTS; PROGRAMMED DEATH-1; Immunology; ANTI-PD-1 ANTIBODY; DISEASE PROGRESSION
• Research Categories: Health Sciences, Medicine and Surgery; Biology, Microbiology; Health Sciences, Immunology

Abstract

PD-1 is an inhibitory receptor induced in T cells by antigen stimulation and sustained PD-1 expression plays a key role in T cell dysfunction. Blocking PD-1 signaling rescues exhausted T cells and is an effective treatment for chronic infections and cancer. Nonetheless, combining PD-1 pathway blockade to therapeutic vaccination should further improve T cell rescue. PD-1 is induced shortly after T cell priming, but little is known about the role of PD-1 in the initiation of immune responses. In addition, the PD-1 pathway may also modulate humoral responses, since both B cells and Tfh cells express PD-1. Therefore, even though much progress has been achieved by manipulation of the PD-1 pathway to rescue exhausted T cells, this powerful immunotherapy could still be further exploited.