Regulation and Function of the PD-L1 Checkpoint

Expression of programmed death-ligand 1 (PD-L1) is frequently observed in human cancers. Binding of PD-L1 to its receptor PD-1 on activated T cells inhibits anti-tumor immunity by counteracting T cell-activating signals. Antibody-based PD-1-PD-L1 inhibitors can induce durable tumor remissions in pat...

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Veröffentlicht in:Immunity (Cambridge, Mass.) Jg. 48; H. 3; S. 434
Hauptverfasser: Sun, Chong, Mezzadra, Riccardo, Schumacher, Ton N
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 20.03.2018
Schlagworte:
Animals
B7-H1 Antigen - antagonists & inhibitors
B7-H1 Antigen - physiology
Gene Expression Regulation
Humans
Immunotherapy
Lymphocyte Activation - drug effects
Lymphocyte Activation - genetics
Lymphocyte Activation - immunology
Molecular Targeted Therapy
Neoplasms - etiology
Neoplasms - metabolism
Neoplasms - therapy
Programmed Cell Death 1 Receptor - metabolism
Signal Transduction
T-Lymphocytes - drug effects
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
ISSN:1097-4180, 1097-4180
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Zusammenfassung:Expression of programmed death-ligand 1 (PD-L1) is frequently observed in human cancers. Binding of PD-L1 to its receptor PD-1 on activated T cells inhibits anti-tumor immunity by counteracting T cell-activating signals. Antibody-based PD-1-PD-L1 inhibitors can induce durable tumor remissions in patients with diverse advanced cancers, and thus expression of PD-L1 on tumor cells and other cells in the tumor microenviroment is of major clinical relevance. Here we review the roles of the PD-1-PD-L1 axis in cancer, focusing on recent findings on the mechanisms that regulate PD-L1 expression at the transcriptional, posttranscriptional, and protein level. We place this knowledge in the context of observations in the clinic and discuss how it may inform the design of more precise and effective cancer immune checkpoint therapies.
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ISSN:1097-4180
1097-4180
DOI:10.1016/j.immuni.2018.03.014