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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Vydané v:	Immunity (Cambridge, Mass.) Ročník 48; číslo 3; s. 434
Hlavní autori:	Sun, Chong, Mezzadra, Riccardo, Schumacher, Ton N
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States 20.03.2018
Predmet:	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
On-line prístup:	Zistit podrobnosti o prístupe
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Abstract	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.
AbstractList	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.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. 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.
Author	Mezzadra, Riccardo Sun, Chong Schumacher, Ton N
Author_xml	– sequence: 1 givenname: Chong surname: Sun fullname: Sun, Chong organization: Division of Molecular Oncology & Immunology, Oncode Institute, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands – sequence: 2 givenname: Riccardo surname: Mezzadra fullname: Mezzadra, Riccardo organization: Division of Molecular Oncology & Immunology, Oncode Institute, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands – sequence: 3 givenname: Ton N surname: Schumacher fullname: Schumacher, Ton N email: t.schumacher@nki.nl organization: Division of Molecular Oncology & Immunology, Oncode Institute, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands. Electronic address: t.schumacher@nki.nl
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/29562194$$D View this record in MEDLINE/PubMed
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Snippet	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... 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...
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SubjectTerms	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
Title	Regulation and Function of the PD-L1 Checkpoint
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