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IFN-γ is required for cytotoxic T cell-dependent cancer genome immunoediting
Genetic evolution that occurs during cancer progression enables tumour heterogeneity, thereby fostering tumour adaptation, therapeutic resistance and metastatic potential. Immune responses are known to select (immunoedit) tumour cells displaying immunoevasive properties. Here we address the role of...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5333095/ https://www.ncbi.nlm.nih.gov/pubmed/28233863 http://dx.doi.org/10.1038/ncomms14607 |
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author | Takeda, Kazuyoshi Nakayama, Masafumi Hayakawa, Yoshihiro Kojima, Yuko Ikeda, Hiroaki Imai, Naoko Ogasawara, Kouetsu Okumura, Ko Thomas, David M. Smyth, Mark J. |
author_facet | Takeda, Kazuyoshi Nakayama, Masafumi Hayakawa, Yoshihiro Kojima, Yuko Ikeda, Hiroaki Imai, Naoko Ogasawara, Kouetsu Okumura, Ko Thomas, David M. Smyth, Mark J. |
author_sort | Takeda, Kazuyoshi |
collection | PubMed |
description | Genetic evolution that occurs during cancer progression enables tumour heterogeneity, thereby fostering tumour adaptation, therapeutic resistance and metastatic potential. Immune responses are known to select (immunoedit) tumour cells displaying immunoevasive properties. Here we address the role of IFN-γ in mediating the immunoediting process. We observe that, in several mouse tumour models such as HA-expressing 4T1 mammary carcinoma cells, OVA-expressing EG7 lymphoma cells and CMS5 MCA-induced fibrosarcoma cells naturally expressing mutated extracellular signal-regulated kinase (ERK) antigen, the action of antigen-specific cytotoxic T cell (CTL) in vivo results in the emergence of resistant cancer cell clones only in the presence of IFN-γ within the tumour microenvironment. Moreover, we show that exposure of tumours to IFN-γ-producing antigen-specific CTLs in vivo results in copy-number alterations (CNAs) associated with DNA damage response and modulation of DNA editing/repair gene expression. These results suggest that enhanced genetic instability might be one of the mechanisms by which CTLs and IFN-γ immunoedits tumours, altering their immune resistance as a result of genetic evolution. |
format | Online Article Text |
id | pubmed-5333095 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-53330952017-03-06 IFN-γ is required for cytotoxic T cell-dependent cancer genome immunoediting Takeda, Kazuyoshi Nakayama, Masafumi Hayakawa, Yoshihiro Kojima, Yuko Ikeda, Hiroaki Imai, Naoko Ogasawara, Kouetsu Okumura, Ko Thomas, David M. Smyth, Mark J. Nat Commun Article Genetic evolution that occurs during cancer progression enables tumour heterogeneity, thereby fostering tumour adaptation, therapeutic resistance and metastatic potential. Immune responses are known to select (immunoedit) tumour cells displaying immunoevasive properties. Here we address the role of IFN-γ in mediating the immunoediting process. We observe that, in several mouse tumour models such as HA-expressing 4T1 mammary carcinoma cells, OVA-expressing EG7 lymphoma cells and CMS5 MCA-induced fibrosarcoma cells naturally expressing mutated extracellular signal-regulated kinase (ERK) antigen, the action of antigen-specific cytotoxic T cell (CTL) in vivo results in the emergence of resistant cancer cell clones only in the presence of IFN-γ within the tumour microenvironment. Moreover, we show that exposure of tumours to IFN-γ-producing antigen-specific CTLs in vivo results in copy-number alterations (CNAs) associated with DNA damage response and modulation of DNA editing/repair gene expression. These results suggest that enhanced genetic instability might be one of the mechanisms by which CTLs and IFN-γ immunoedits tumours, altering their immune resistance as a result of genetic evolution. Nature Publishing Group 2017-02-24 /pmc/articles/PMC5333095/ /pubmed/28233863 http://dx.doi.org/10.1038/ncomms14607 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Takeda, Kazuyoshi Nakayama, Masafumi Hayakawa, Yoshihiro Kojima, Yuko Ikeda, Hiroaki Imai, Naoko Ogasawara, Kouetsu Okumura, Ko Thomas, David M. Smyth, Mark J. IFN-γ is required for cytotoxic T cell-dependent cancer genome immunoediting |
title | IFN-γ is required for cytotoxic T cell-dependent cancer genome immunoediting |
title_full | IFN-γ is required for cytotoxic T cell-dependent cancer genome immunoediting |
title_fullStr | IFN-γ is required for cytotoxic T cell-dependent cancer genome immunoediting |
title_full_unstemmed | IFN-γ is required for cytotoxic T cell-dependent cancer genome immunoediting |
title_short | IFN-γ is required for cytotoxic T cell-dependent cancer genome immunoediting |
title_sort | ifn-γ is required for cytotoxic t cell-dependent cancer genome immunoediting |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5333095/ https://www.ncbi.nlm.nih.gov/pubmed/28233863 http://dx.doi.org/10.1038/ncomms14607 |
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