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The Molecular and Functional Characteristics of HLA-G and the Interaction with Its Receptors: Where to Intervene for Cancer Immunotherapy?

Human leukocyte antigen G (HLA-G) mediates maternal-fetal immune tolerance. It is also considered an immune checkpoint in cancer since it may mediate immune evasion and thus promote tumor growth. HLA-G is, therefore, a potential target for immunotherapy. However, existing monoclonal antibodies direc...

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Autores principales: Attia, Jiji V. D., Dessens, Charlotte E., van de Water, Ricky, Houvast, Ruben D., Kuppen, Peter J. K., Krijgsman, Daniëlle
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698525/
https://www.ncbi.nlm.nih.gov/pubmed/33213057
http://dx.doi.org/10.3390/ijms21228678
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author Attia, Jiji V. D.
Dessens, Charlotte E.
van de Water, Ricky
Houvast, Ruben D.
Kuppen, Peter J. K.
Krijgsman, Daniëlle
author_facet Attia, Jiji V. D.
Dessens, Charlotte E.
van de Water, Ricky
Houvast, Ruben D.
Kuppen, Peter J. K.
Krijgsman, Daniëlle
author_sort Attia, Jiji V. D.
collection PubMed
description Human leukocyte antigen G (HLA-G) mediates maternal-fetal immune tolerance. It is also considered an immune checkpoint in cancer since it may mediate immune evasion and thus promote tumor growth. HLA-G is, therefore, a potential target for immunotherapy. However, existing monoclonal antibodies directed against HLA-G lack sufficient specificity and are not suitable for immune checkpoint inhibition in a clinical setting. For this reason, it is essential that alternative approaches are explored to block the interaction between HLA-G and its receptors. In this review, we discuss the structure and peptide presentation of HLA-G, and its interaction with the receptors Ig-like transcript (ILT) 2, ILT4, and Killer cell immunoglobulin-like receptor 2DL4 (KIR2DL4). Based on our findings, we propose three alternative strategies to block the interaction between HLA-G and its receptors in cancer immunotherapy: (1) prevention of HLA-G dimerization, (2) targeting the peptide-binding groove of HLA-G, and (3) targeting the HLA-G receptors. These strategies should be an important focus of future studies that aim to develop immune checkpoint inhibitors to block the interaction between HLA-G and its receptors for the treatment of cancer.
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spelling pubmed-76985252020-11-29 The Molecular and Functional Characteristics of HLA-G and the Interaction with Its Receptors: Where to Intervene for Cancer Immunotherapy? Attia, Jiji V. D. Dessens, Charlotte E. van de Water, Ricky Houvast, Ruben D. Kuppen, Peter J. K. Krijgsman, Daniëlle Int J Mol Sci Review Human leukocyte antigen G (HLA-G) mediates maternal-fetal immune tolerance. It is also considered an immune checkpoint in cancer since it may mediate immune evasion and thus promote tumor growth. HLA-G is, therefore, a potential target for immunotherapy. However, existing monoclonal antibodies directed against HLA-G lack sufficient specificity and are not suitable for immune checkpoint inhibition in a clinical setting. For this reason, it is essential that alternative approaches are explored to block the interaction between HLA-G and its receptors. In this review, we discuss the structure and peptide presentation of HLA-G, and its interaction with the receptors Ig-like transcript (ILT) 2, ILT4, and Killer cell immunoglobulin-like receptor 2DL4 (KIR2DL4). Based on our findings, we propose three alternative strategies to block the interaction between HLA-G and its receptors in cancer immunotherapy: (1) prevention of HLA-G dimerization, (2) targeting the peptide-binding groove of HLA-G, and (3) targeting the HLA-G receptors. These strategies should be an important focus of future studies that aim to develop immune checkpoint inhibitors to block the interaction between HLA-G and its receptors for the treatment of cancer. MDPI 2020-11-17 /pmc/articles/PMC7698525/ /pubmed/33213057 http://dx.doi.org/10.3390/ijms21228678 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Attia, Jiji V. D.
Dessens, Charlotte E.
van de Water, Ricky
Houvast, Ruben D.
Kuppen, Peter J. K.
Krijgsman, Daniëlle
The Molecular and Functional Characteristics of HLA-G and the Interaction with Its Receptors: Where to Intervene for Cancer Immunotherapy?
title The Molecular and Functional Characteristics of HLA-G and the Interaction with Its Receptors: Where to Intervene for Cancer Immunotherapy?
title_full The Molecular and Functional Characteristics of HLA-G and the Interaction with Its Receptors: Where to Intervene for Cancer Immunotherapy?
title_fullStr The Molecular and Functional Characteristics of HLA-G and the Interaction with Its Receptors: Where to Intervene for Cancer Immunotherapy?
title_full_unstemmed The Molecular and Functional Characteristics of HLA-G and the Interaction with Its Receptors: Where to Intervene for Cancer Immunotherapy?
title_short The Molecular and Functional Characteristics of HLA-G and the Interaction with Its Receptors: Where to Intervene for Cancer Immunotherapy?
title_sort molecular and functional characteristics of hla-g and the interaction with its receptors: where to intervene for cancer immunotherapy?
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698525/
https://www.ncbi.nlm.nih.gov/pubmed/33213057
http://dx.doi.org/10.3390/ijms21228678
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