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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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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. |
format | Online Article Text |
id | pubmed-7698525 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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