The diverse functions of the PD1 inhibitory pathway

T cell activation is a highly regulated process involving peptide-MHC engagement of the T cell receptor and positive costimulatory signals. Upon activation, coinhibitory 'checkpoints', including programmed cell death protein 1 (PD1), become induced to regulate T cells. PD1 has an essential...

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Bibliographic Details
Published in:Nature reviews. Immunology Vol. 18; no. 3; pp. 153 - 167
Main Authors: Sharpe, Arlene H, Pauken, Kristen E
Format: Journal Article
Language:English
Published: England Nature Publishing Group 01.03.2018
Subjects:
Antibodies, Monoclonal - therapeutic use
Antineoplastic Agents, Immunological - therapeutic use
Apoptosis
Autoimmunity
Autoimmunity - immunology
B-Lymphocytes - immunology
Cancer
Cancer immunotherapy
CD4 antigen
CD8 antigen
Cell activation
Cell death
Chronic infection
Homeostasis
Humans
Immune checkpoint
Immune response
Immunological tolerance
Immunoregulation
Immunotherapy
Immunotherapy - methods
Killer Cells, Natural - immunology
Lymphocyte Activation - immunology
Lymphocytes
Lymphocytes B
Lymphocytes T
Lymphoid tissue
Major histocompatibility complex
Mortality
Natural killer cells
Neoplasms - drug therapy
Patients
PD-1 protein
Physiological responses
Programmed Cell Death 1 Receptor - antagonists & inhibitors
Programmed Cell Death 1 Receptor - metabolism
Signal Transduction - immunology
T cell receptors
T-Lymphocytes - immunology
Transplantation
Tumors
ISSN:1474-1733, 1474-1741, 1474-1741
Online Access:Get full text
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Summary:T cell activation is a highly regulated process involving peptide-MHC engagement of the T cell receptor and positive costimulatory signals. Upon activation, coinhibitory 'checkpoints', including programmed cell death protein 1 (PD1), become induced to regulate T cells. PD1 has an essential role in balancing protective immunity and immunopathology, homeostasis and tolerance. However, during responses to chronic pathogens and tumours, PD1 expression can limit protective immunity. Recently developed PD1 pathway inhibitors have revolutionized cancer treatment for some patients, but the majority of patients do not show complete responses, and adverse events have been noted. This Review discusses the diverse roles of the PD1 pathway in regulating immune responses and how this knowledge can improve cancer immunotherapy as well as restore and/or maintain tolerance during autoimmunity and transplantation.
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ISSN:1474-1733
1474-1741
1474-1741
DOI:10.1038/nri.2017.108