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Mechanism of action of PD‐1 receptor/ligand targeted cancer immunotherapy [Image: see text]

Immunotherapy targeting the Programmed Death (PD‐1) receptor/ligand (L) “checkpoint” rapidly gains ground in the treatment of many cancer types. To increase treatment scope and efficacy, predictive biomarkers and rational selection of co‐treatments are required. To meet these demands, we must unders...

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Autores principales: Borst, Jannie, Busselaar, Julia, Bosma, Douwe M. T., Ossendorp, Ferry
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8453912/
https://www.ncbi.nlm.nih.gov/pubmed/34106465
http://dx.doi.org/10.1002/eji.202048994
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author Borst, Jannie
Busselaar, Julia
Bosma, Douwe M. T.
Ossendorp, Ferry
author_facet Borst, Jannie
Busselaar, Julia
Bosma, Douwe M. T.
Ossendorp, Ferry
author_sort Borst, Jannie
collection PubMed
description Immunotherapy targeting the Programmed Death (PD‐1) receptor/ligand (L) “checkpoint” rapidly gains ground in the treatment of many cancer types. To increase treatment scope and efficacy, predictive biomarkers and rational selection of co‐treatments are required. To meet these demands, we must understand PD‐1 function in detail. We here outline recent insights into the regulation of the CD8(+) T cell response by PD‐1. The prevailing view has been that blockade of PD‐1/ligand (L) interaction “reinvigorates” cytotoxic T lymphocytes (CTL) that were rendered dysfunctional in the tumor microenvironment (TME). However, this review stresses that tumors continuously communicate with adjacent draining lymph nodes (LNs) and that the PD‐1 checkpoint also operates during T cell priming. We clarify the role of the PD‐(L)1 system at the T cell/DC interface, where it regulates T cell receptor (TCR) signaling and CD28 costimulation and thus controls activation of tumor‐specific T cells. We also highlight the importance of CD4(+) T cell help during priming, which allows DCs to provide other costimulatory and cytokine signals required for optimal CTL differentiation and likely avoidance of a dysfunctional state. Therefore, we pose that PD‐(L)1 blockade should exploit LN function and be combined with “help” signals to optimize CTL efficacy.
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spelling pubmed-84539122021-09-27 Mechanism of action of PD‐1 receptor/ligand targeted cancer immunotherapy [Image: see text] Borst, Jannie Busselaar, Julia Bosma, Douwe M. T. Ossendorp, Ferry Eur J Immunol Highlights Immunotherapy targeting the Programmed Death (PD‐1) receptor/ligand (L) “checkpoint” rapidly gains ground in the treatment of many cancer types. To increase treatment scope and efficacy, predictive biomarkers and rational selection of co‐treatments are required. To meet these demands, we must understand PD‐1 function in detail. We here outline recent insights into the regulation of the CD8(+) T cell response by PD‐1. The prevailing view has been that blockade of PD‐1/ligand (L) interaction “reinvigorates” cytotoxic T lymphocytes (CTL) that were rendered dysfunctional in the tumor microenvironment (TME). However, this review stresses that tumors continuously communicate with adjacent draining lymph nodes (LNs) and that the PD‐1 checkpoint also operates during T cell priming. We clarify the role of the PD‐(L)1 system at the T cell/DC interface, where it regulates T cell receptor (TCR) signaling and CD28 costimulation and thus controls activation of tumor‐specific T cells. We also highlight the importance of CD4(+) T cell help during priming, which allows DCs to provide other costimulatory and cytokine signals required for optimal CTL differentiation and likely avoidance of a dysfunctional state. Therefore, we pose that PD‐(L)1 blockade should exploit LN function and be combined with “help” signals to optimize CTL efficacy. John Wiley and Sons Inc. 2021-06-21 2021-08 /pmc/articles/PMC8453912/ /pubmed/34106465 http://dx.doi.org/10.1002/eji.202048994 Text en © 2021 The Authors. European Journal of Immunology published by Wiley‐VCH GmbH https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Highlights
Borst, Jannie
Busselaar, Julia
Bosma, Douwe M. T.
Ossendorp, Ferry
Mechanism of action of PD‐1 receptor/ligand targeted cancer immunotherapy [Image: see text]
title Mechanism of action of PD‐1 receptor/ligand targeted cancer immunotherapy [Image: see text]
title_full Mechanism of action of PD‐1 receptor/ligand targeted cancer immunotherapy [Image: see text]
title_fullStr Mechanism of action of PD‐1 receptor/ligand targeted cancer immunotherapy [Image: see text]
title_full_unstemmed Mechanism of action of PD‐1 receptor/ligand targeted cancer immunotherapy [Image: see text]
title_short Mechanism of action of PD‐1 receptor/ligand targeted cancer immunotherapy [Image: see text]
title_sort mechanism of action of pd‐1 receptor/ligand targeted cancer immunotherapy [image: see text]
topic Highlights
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8453912/
https://www.ncbi.nlm.nih.gov/pubmed/34106465
http://dx.doi.org/10.1002/eji.202048994
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