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The promising immune checkpoint LAG-3: from tumor microenvironment to cancer immunotherapy

Cancer immunotherapy and tumor microenvironment have been at the forefront of research over the past decades. Targeting immune checkpoints especially programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) has made a breakthrough in treating advanced malignancies. However, the low response rate...

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Autores principales: Long, Long, Zhang, Xue, Chen, Fuchun, Pan, Qi, Phiphatwatchara, Pronnaphat, Zeng, Yuyang, Chen, Honglei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305110/
https://www.ncbi.nlm.nih.gov/pubmed/30603054
http://dx.doi.org/10.18632/genesandcancer.180
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author Long, Long
Zhang, Xue
Chen, Fuchun
Pan, Qi
Phiphatwatchara, Pronnaphat
Zeng, Yuyang
Chen, Honglei
author_facet Long, Long
Zhang, Xue
Chen, Fuchun
Pan, Qi
Phiphatwatchara, Pronnaphat
Zeng, Yuyang
Chen, Honglei
author_sort Long, Long
collection PubMed
description Cancer immunotherapy and tumor microenvironment have been at the forefront of research over the past decades. Targeting immune checkpoints especially programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) has made a breakthrough in treating advanced malignancies. However, the low response rate brings a daunting challenge, changing the focus to dig deeply into the tumor microenvironment for alternative therapeutic targets. Strikingly, the inhibitory immune checkpoint lymphocyte activation gene-3 (LAG-3) holds considerable potential. LAG-3 suppresses T cells activation and cytokines secretion, thereby ensuring immune homeostasis. It exerts differential inhibitory impacts on various types of lymphocytes and shows a remarkable synergy with PD-1 to inhibit immune responses. Targeting LAG-3 immunotherapy is moving forward in active clinical trials, and combination immunotherapy of anti-LAG-3 and anti-PD-1 has shown exciting efficacy in fighting PD-1 resistance. Herein, we shed light on the significance of LAG-3 in the tumor microenvironment, highlight its role to regulate different lymphocytes, interplay with other immune checkpoints especially PD-1, and emphasize new advances in LAG-3-targeted immunotherapy.
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spelling pubmed-63051102019-01-02 The promising immune checkpoint LAG-3: from tumor microenvironment to cancer immunotherapy Long, Long Zhang, Xue Chen, Fuchun Pan, Qi Phiphatwatchara, Pronnaphat Zeng, Yuyang Chen, Honglei Genes Cancer Review Cancer immunotherapy and tumor microenvironment have been at the forefront of research over the past decades. Targeting immune checkpoints especially programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) has made a breakthrough in treating advanced malignancies. However, the low response rate brings a daunting challenge, changing the focus to dig deeply into the tumor microenvironment for alternative therapeutic targets. Strikingly, the inhibitory immune checkpoint lymphocyte activation gene-3 (LAG-3) holds considerable potential. LAG-3 suppresses T cells activation and cytokines secretion, thereby ensuring immune homeostasis. It exerts differential inhibitory impacts on various types of lymphocytes and shows a remarkable synergy with PD-1 to inhibit immune responses. Targeting LAG-3 immunotherapy is moving forward in active clinical trials, and combination immunotherapy of anti-LAG-3 and anti-PD-1 has shown exciting efficacy in fighting PD-1 resistance. Herein, we shed light on the significance of LAG-3 in the tumor microenvironment, highlight its role to regulate different lymphocytes, interplay with other immune checkpoints especially PD-1, and emphasize new advances in LAG-3-targeted immunotherapy. Impact Journals LLC 2018-05 /pmc/articles/PMC6305110/ /pubmed/30603054 http://dx.doi.org/10.18632/genesandcancer.180 Text en Copyright: © 2018 Long et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Review
Long, Long
Zhang, Xue
Chen, Fuchun
Pan, Qi
Phiphatwatchara, Pronnaphat
Zeng, Yuyang
Chen, Honglei
The promising immune checkpoint LAG-3: from tumor microenvironment to cancer immunotherapy
title The promising immune checkpoint LAG-3: from tumor microenvironment to cancer immunotherapy
title_full The promising immune checkpoint LAG-3: from tumor microenvironment to cancer immunotherapy
title_fullStr The promising immune checkpoint LAG-3: from tumor microenvironment to cancer immunotherapy
title_full_unstemmed The promising immune checkpoint LAG-3: from tumor microenvironment to cancer immunotherapy
title_short The promising immune checkpoint LAG-3: from tumor microenvironment to cancer immunotherapy
title_sort promising immune checkpoint lag-3: from tumor microenvironment to cancer immunotherapy
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305110/
https://www.ncbi.nlm.nih.gov/pubmed/30603054
http://dx.doi.org/10.18632/genesandcancer.180
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