Modeling tumor immunity of mouse glioblastoma by exhausted CD8(+) T cells
T cell exhaustion occurs during chronic infection and cancers. Programmed cell death protein-1 (PD-1) is a major inhibitory checkpoint receptor involved in T cell exhaustion. Blocking antibodies (Abs) against PD-1 or its ligand, PD-L1, have been shown to reverse T cell exhaustion during chronic infe...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5760520/ https://www.ncbi.nlm.nih.gov/pubmed/29317703 http://dx.doi.org/10.1038/s41598-017-18540-2 |
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author | Nakashima, Hiroshi Alayo, Quazim A. Penaloza-MacMaster, Pablo Freeman, Gordon J. Kuchroo, Vijay K. Reardon, David A. Fernandez, Soledad Caligiuri, Michael Chiocca, E. Antonio |
author_facet | Nakashima, Hiroshi Alayo, Quazim A. Penaloza-MacMaster, Pablo Freeman, Gordon J. Kuchroo, Vijay K. Reardon, David A. Fernandez, Soledad Caligiuri, Michael Chiocca, E. Antonio |
author_sort | Nakashima, Hiroshi |
collection | PubMed |
description | T cell exhaustion occurs during chronic infection and cancers. Programmed cell death protein-1 (PD-1) is a major inhibitory checkpoint receptor involved in T cell exhaustion. Blocking antibodies (Abs) against PD-1 or its ligand, PD-L1, have been shown to reverse T cell exhaustion during chronic infection and cancers, leading to improved control of persistent antigen. However, modeling tumor-specific T cell responses in mouse has been difficult due to the lack of reagents to detect and phenotype tumor-specific immune responses. We developed a novel mouse glioma model expressing a viral epitope derived from lymphocytic choriomeningitis virus (LCMV), which allowed monitoring of tumor-specific CD8 T-cell responses. These CD8 T cells express high levels of PD-1 and are unable to reject tumors, but this can be reversed by anti-PD-1 treatment. These results suggest the efficacy of PD-1 blockade as a treatment for glioblastoma, an aggressive tumor that results in a uniformly lethal outcome. Importantly, this new syngeneic tumor model may also provide further opportunities to characterize anti-tumor T cell exhaustion and develop novel cancer immunotherapies. |
format | Online Article Text |
id | pubmed-5760520 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-57605202018-01-17 Modeling tumor immunity of mouse glioblastoma by exhausted CD8(+) T cells Nakashima, Hiroshi Alayo, Quazim A. Penaloza-MacMaster, Pablo Freeman, Gordon J. Kuchroo, Vijay K. Reardon, David A. Fernandez, Soledad Caligiuri, Michael Chiocca, E. Antonio Sci Rep Article T cell exhaustion occurs during chronic infection and cancers. Programmed cell death protein-1 (PD-1) is a major inhibitory checkpoint receptor involved in T cell exhaustion. Blocking antibodies (Abs) against PD-1 or its ligand, PD-L1, have been shown to reverse T cell exhaustion during chronic infection and cancers, leading to improved control of persistent antigen. However, modeling tumor-specific T cell responses in mouse has been difficult due to the lack of reagents to detect and phenotype tumor-specific immune responses. We developed a novel mouse glioma model expressing a viral epitope derived from lymphocytic choriomeningitis virus (LCMV), which allowed monitoring of tumor-specific CD8 T-cell responses. These CD8 T cells express high levels of PD-1 and are unable to reject tumors, but this can be reversed by anti-PD-1 treatment. These results suggest the efficacy of PD-1 blockade as a treatment for glioblastoma, an aggressive tumor that results in a uniformly lethal outcome. Importantly, this new syngeneic tumor model may also provide further opportunities to characterize anti-tumor T cell exhaustion and develop novel cancer immunotherapies. Nature Publishing Group UK 2018-01-09 /pmc/articles/PMC5760520/ /pubmed/29317703 http://dx.doi.org/10.1038/s41598-017-18540-2 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Nakashima, Hiroshi Alayo, Quazim A. Penaloza-MacMaster, Pablo Freeman, Gordon J. Kuchroo, Vijay K. Reardon, David A. Fernandez, Soledad Caligiuri, Michael Chiocca, E. Antonio Modeling tumor immunity of mouse glioblastoma by exhausted CD8(+) T cells |
title | Modeling tumor immunity of mouse glioblastoma by exhausted CD8(+) T cells |
title_full | Modeling tumor immunity of mouse glioblastoma by exhausted CD8(+) T cells |
title_fullStr | Modeling tumor immunity of mouse glioblastoma by exhausted CD8(+) T cells |
title_full_unstemmed | Modeling tumor immunity of mouse glioblastoma by exhausted CD8(+) T cells |
title_short | Modeling tumor immunity of mouse glioblastoma by exhausted CD8(+) T cells |
title_sort | modeling tumor immunity of mouse glioblastoma by exhausted cd8(+) t cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5760520/ https://www.ncbi.nlm.nih.gov/pubmed/29317703 http://dx.doi.org/10.1038/s41598-017-18540-2 |
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