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Impaired gp100-Specific CD8(+) T-Cell Responses in the Presence of Myeloid-Derived Suppressor Cells in a Spontaneous Mouse Melanoma Model
Murine tumor models that closely reflect human diseases are important tools to investigate carcinogenesis and tumor immunity. The transgenic (tg) mouse strain tg(Grm1)EPv develops spontaneous melanoma due to ectopic overexpression of the metabotropic glutamate receptor 1 (Grm1) in melanocytes. In th...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4652066/ https://www.ncbi.nlm.nih.gov/pubmed/26121214 http://dx.doi.org/10.1038/jid.2015.241 |
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author | Mairhofer, David G Ortner, Daniela Tripp, Christoph H Schaffenrath, Sandra Fleming, Viktor Heger, Lukas Komenda, Kerstin Reider, Daniela Dudziak, Diana Chen, Suzie Becker, Jürgen C Flacher, Vincent Stoitzner, Patrizia |
author_facet | Mairhofer, David G Ortner, Daniela Tripp, Christoph H Schaffenrath, Sandra Fleming, Viktor Heger, Lukas Komenda, Kerstin Reider, Daniela Dudziak, Diana Chen, Suzie Becker, Jürgen C Flacher, Vincent Stoitzner, Patrizia |
author_sort | Mairhofer, David G |
collection | PubMed |
description | Murine tumor models that closely reflect human diseases are important tools to investigate carcinogenesis and tumor immunity. The transgenic (tg) mouse strain tg(Grm1)EPv develops spontaneous melanoma due to ectopic overexpression of the metabotropic glutamate receptor 1 (Grm1) in melanocytes. In the present study, we characterized the immune status and functional properties of immune cells in tumor-bearing mice. Melanoma development was accompanied by a reduction in the percentages of CD4(+) T cells including regulatory T cells (Tregs) in CD45(+) leukocytes present in tumor tissue and draining lymph nodes (LNs). In contrast, the percentages of CD8(+) T cells were unchanged, and these cells showed an activated phenotype in tumor mice. Endogenous melanoma-associated antigen glycoprotein 100 (gp100)-specific CD8(+) T cells were not deleted during tumor development, as revealed by pentamer staining in the skin and draining LNs. They, however, were unresponsive to ex vivo gp100-peptide stimulation in late-stage tumor mice. Interestingly, immunosuppressive myeloid-derived suppressor cells (MDSCs) were recruited to tumor tissue with a preferential accumulation of granulocytic MDSC (grMDSCs) over monocytic MDSC (moMDSCs). Both subsets produced Arginase-1, inducible nitric oxide synthase (iNOS), and transforming growth factor-β and suppressed T-cell proliferation in vitro. In this work, we describe the immune status of a spontaneous melanoma mouse model that provides an interesting tool to develop future immunotherapeutical strategies. |
format | Online Article Text |
id | pubmed-4652066 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-46520662015-12-04 Impaired gp100-Specific CD8(+) T-Cell Responses in the Presence of Myeloid-Derived Suppressor Cells in a Spontaneous Mouse Melanoma Model Mairhofer, David G Ortner, Daniela Tripp, Christoph H Schaffenrath, Sandra Fleming, Viktor Heger, Lukas Komenda, Kerstin Reider, Daniela Dudziak, Diana Chen, Suzie Becker, Jürgen C Flacher, Vincent Stoitzner, Patrizia J Invest Dermatol Original Article Murine tumor models that closely reflect human diseases are important tools to investigate carcinogenesis and tumor immunity. The transgenic (tg) mouse strain tg(Grm1)EPv develops spontaneous melanoma due to ectopic overexpression of the metabotropic glutamate receptor 1 (Grm1) in melanocytes. In the present study, we characterized the immune status and functional properties of immune cells in tumor-bearing mice. Melanoma development was accompanied by a reduction in the percentages of CD4(+) T cells including regulatory T cells (Tregs) in CD45(+) leukocytes present in tumor tissue and draining lymph nodes (LNs). In contrast, the percentages of CD8(+) T cells were unchanged, and these cells showed an activated phenotype in tumor mice. Endogenous melanoma-associated antigen glycoprotein 100 (gp100)-specific CD8(+) T cells were not deleted during tumor development, as revealed by pentamer staining in the skin and draining LNs. They, however, were unresponsive to ex vivo gp100-peptide stimulation in late-stage tumor mice. Interestingly, immunosuppressive myeloid-derived suppressor cells (MDSCs) were recruited to tumor tissue with a preferential accumulation of granulocytic MDSC (grMDSCs) over monocytic MDSC (moMDSCs). Both subsets produced Arginase-1, inducible nitric oxide synthase (iNOS), and transforming growth factor-β and suppressed T-cell proliferation in vitro. In this work, we describe the immune status of a spontaneous melanoma mouse model that provides an interesting tool to develop future immunotherapeutical strategies. Nature Publishing Group 2015-11 2015-07-30 /pmc/articles/PMC4652066/ /pubmed/26121214 http://dx.doi.org/10.1038/jid.2015.241 Text en Copyright © 2015 The Society for Investigative Dermatology, Inc http://creativecommons.org/licenses/by-nc-sa/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 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-nc-sa/4.0/ |
spellingShingle | Original Article Mairhofer, David G Ortner, Daniela Tripp, Christoph H Schaffenrath, Sandra Fleming, Viktor Heger, Lukas Komenda, Kerstin Reider, Daniela Dudziak, Diana Chen, Suzie Becker, Jürgen C Flacher, Vincent Stoitzner, Patrizia Impaired gp100-Specific CD8(+) T-Cell Responses in the Presence of Myeloid-Derived Suppressor Cells in a Spontaneous Mouse Melanoma Model |
title | Impaired gp100-Specific CD8(+) T-Cell Responses in the Presence of Myeloid-Derived Suppressor Cells in a Spontaneous Mouse Melanoma Model |
title_full | Impaired gp100-Specific CD8(+) T-Cell Responses in the Presence of Myeloid-Derived Suppressor Cells in a Spontaneous Mouse Melanoma Model |
title_fullStr | Impaired gp100-Specific CD8(+) T-Cell Responses in the Presence of Myeloid-Derived Suppressor Cells in a Spontaneous Mouse Melanoma Model |
title_full_unstemmed | Impaired gp100-Specific CD8(+) T-Cell Responses in the Presence of Myeloid-Derived Suppressor Cells in a Spontaneous Mouse Melanoma Model |
title_short | Impaired gp100-Specific CD8(+) T-Cell Responses in the Presence of Myeloid-Derived Suppressor Cells in a Spontaneous Mouse Melanoma Model |
title_sort | impaired gp100-specific cd8(+) t-cell responses in the presence of myeloid-derived suppressor cells in a spontaneous mouse melanoma model |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4652066/ https://www.ncbi.nlm.nih.gov/pubmed/26121214 http://dx.doi.org/10.1038/jid.2015.241 |
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