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The Essential Role of Type I Interferons in Differentiation and Activation of Tumor-Associated Neutrophils
Type I interferons (IFNs) were first characterized in the process of viral interference. However, since then, IFNs are found to be involved in a wide range of biological processes. In the mouse, type I IFNs comprise a large family of cytokines. At least 12 IFN-α and one IFN-β can be found and they a...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2016
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5174087/ https://www.ncbi.nlm.nih.gov/pubmed/28066438 http://dx.doi.org/10.3389/fimmu.2016.00629 |
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author | Pylaeva, Ekaterina Lang, Stephan Jablonska, Jadwiga |
author_facet | Pylaeva, Ekaterina Lang, Stephan Jablonska, Jadwiga |
author_sort | Pylaeva, Ekaterina |
collection | PubMed |
description | Type I interferons (IFNs) were first characterized in the process of viral interference. However, since then, IFNs are found to be involved in a wide range of biological processes. In the mouse, type I IFNs comprise a large family of cytokines. At least 12 IFN-α and one IFN-β can be found and they all signal through the same receptor (IFNAR). A hierarchy of expression has been established for type I IFNs, where IFN-β is induced first and it activates in a paracrine and autocrine fashion a cascade of other type I IFNs. Besides its importance in the induction of the IFN cascade, IFN-β is also constitutively expressed in low amounts under normal non-inflammatory conditions, thus facilitating “primed” state of the immune system. In the context of cancer, type I IFNs show strong antitumor function as they play a key role in mounting antitumor immune responses through the modulation of neutrophil differentiation, activation, and migration. Owing to their plasticity, neutrophils play diverse roles during cancer development and metastasis since they possess both tumor-promoting (N2) and tumor-limiting (N1) properties. Notably, the differentiation into antitumor phenotype is strongly supported by type I IFNs. It could also be shown that these cytokines are critical for the suppression of neutrophil migration into tumor and metastasis site by regulating chemokine receptors, e.g., CXCR2 on these cells and by influencing their longevity. Type I IFNs limit the life span of neutrophils by influencing both, the extrinsic as well as the intrinsic apoptosis pathways. Such antitumor neutrophils efficiently suppress the pro-angiogenic factors expression, e.g., vascular endothelial growth factor and matrix metallopeptidase 9. This in turn restricts tumor vascularization and growth. Thus, type I IFNs appear to be the part of the natural tumor surveillance mechanism. Here we provide an up to date review of how type I IFNs influence the pro- and antitumor properties of neutrophils. Understanding these mechanisms is particularly important from a therapeutic point of view. |
format | Online Article Text |
id | pubmed-5174087 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-51740872017-01-06 The Essential Role of Type I Interferons in Differentiation and Activation of Tumor-Associated Neutrophils Pylaeva, Ekaterina Lang, Stephan Jablonska, Jadwiga Front Immunol Immunology Type I interferons (IFNs) were first characterized in the process of viral interference. However, since then, IFNs are found to be involved in a wide range of biological processes. In the mouse, type I IFNs comprise a large family of cytokines. At least 12 IFN-α and one IFN-β can be found and they all signal through the same receptor (IFNAR). A hierarchy of expression has been established for type I IFNs, where IFN-β is induced first and it activates in a paracrine and autocrine fashion a cascade of other type I IFNs. Besides its importance in the induction of the IFN cascade, IFN-β is also constitutively expressed in low amounts under normal non-inflammatory conditions, thus facilitating “primed” state of the immune system. In the context of cancer, type I IFNs show strong antitumor function as they play a key role in mounting antitumor immune responses through the modulation of neutrophil differentiation, activation, and migration. Owing to their plasticity, neutrophils play diverse roles during cancer development and metastasis since they possess both tumor-promoting (N2) and tumor-limiting (N1) properties. Notably, the differentiation into antitumor phenotype is strongly supported by type I IFNs. It could also be shown that these cytokines are critical for the suppression of neutrophil migration into tumor and metastasis site by regulating chemokine receptors, e.g., CXCR2 on these cells and by influencing their longevity. Type I IFNs limit the life span of neutrophils by influencing both, the extrinsic as well as the intrinsic apoptosis pathways. Such antitumor neutrophils efficiently suppress the pro-angiogenic factors expression, e.g., vascular endothelial growth factor and matrix metallopeptidase 9. This in turn restricts tumor vascularization and growth. Thus, type I IFNs appear to be the part of the natural tumor surveillance mechanism. Here we provide an up to date review of how type I IFNs influence the pro- and antitumor properties of neutrophils. Understanding these mechanisms is particularly important from a therapeutic point of view. Frontiers Media S.A. 2016-12-21 /pmc/articles/PMC5174087/ /pubmed/28066438 http://dx.doi.org/10.3389/fimmu.2016.00629 Text en Copyright © 2016 Pylaeva, Lang and Jablonska. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Pylaeva, Ekaterina Lang, Stephan Jablonska, Jadwiga The Essential Role of Type I Interferons in Differentiation and Activation of Tumor-Associated Neutrophils |
title | The Essential Role of Type I Interferons in Differentiation and Activation of Tumor-Associated Neutrophils |
title_full | The Essential Role of Type I Interferons in Differentiation and Activation of Tumor-Associated Neutrophils |
title_fullStr | The Essential Role of Type I Interferons in Differentiation and Activation of Tumor-Associated Neutrophils |
title_full_unstemmed | The Essential Role of Type I Interferons in Differentiation and Activation of Tumor-Associated Neutrophils |
title_short | The Essential Role of Type I Interferons in Differentiation and Activation of Tumor-Associated Neutrophils |
title_sort | essential role of type i interferons in differentiation and activation of tumor-associated neutrophils |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5174087/ https://www.ncbi.nlm.nih.gov/pubmed/28066438 http://dx.doi.org/10.3389/fimmu.2016.00629 |
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