Phenotypic T cell exhaustion in a murine model of bacterial infection in the setting of pre-existing malignancy.
While much of cancer immunology research has focused on anti-tumor immunity both systemically and within the tumor microenvironment, little is known about the impact of pre-existing malignancy on pathogen-specific immune responses. Here, we sought to characterize the antigen-specific CD8+ T cell res...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24796533/pdf/?tool=EBI |
| _version_ | 1819240675230613504 |
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| author | Rohit Mittal Maylene Wagener Elise R Breed Zhe Liang Benyam P Yoseph Eileen M Burd Alton B Farris Craig M Coopersmith Mandy L Ford |
| author_facet | Rohit Mittal Maylene Wagener Elise R Breed Zhe Liang Benyam P Yoseph Eileen M Burd Alton B Farris Craig M Coopersmith Mandy L Ford |
| author_sort | Rohit Mittal |
| collection | DOAJ |
| description | While much of cancer immunology research has focused on anti-tumor immunity both systemically and within the tumor microenvironment, little is known about the impact of pre-existing malignancy on pathogen-specific immune responses. Here, we sought to characterize the antigen-specific CD8+ T cell response following a bacterial infection in the setting of pre-existing pancreatic adenocarcinoma. Mice with established subcutaneous pancreatic adenocarcinomas were infected with Listeria monocytogenes, and antigen-specific CD8+ T cell responses were compared to those in control mice without cancer. While the kinetics and magnitude of antigen-specific CD8+ T cell expansion and accumulation was comparable between the cancer and non-cancer groups, bacterial antigen-specific CD8+ T cells and total CD4+ and CD8+ T cells in cancer mice exhibited increased expression of the coinhibitory receptors BTLA, PD-1, and 2B4. Furthermore, increased inhibitory receptor expression was associated with reduced IFN-γ and increased IL-2 production by bacterial antigen-specific CD8+ T cells in the cancer group. Taken together, these data suggest that cancer's immune suppressive effects are not limited to the tumor microenvironment, but that pre-existing malignancy induces phenotypic exhaustion in T cells by increasing expression of coinhibitory receptors and may impair pathogen-specific CD8+ T cell functionality and differentiation. |
| first_indexed | 2024-12-23T14:11:47Z |
| format | Article |
| id | doaj.art-31e83b4735fe437e86aaef097708f8e5 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T14:11:47Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-31e83b4735fe437e86aaef097708f8e52022-12-21T17:44:01ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0195e9352310.1371/journal.pone.0093523Phenotypic T cell exhaustion in a murine model of bacterial infection in the setting of pre-existing malignancy.Rohit MittalMaylene WagenerElise R BreedZhe LiangBenyam P YosephEileen M BurdAlton B FarrisCraig M CoopersmithMandy L FordWhile much of cancer immunology research has focused on anti-tumor immunity both systemically and within the tumor microenvironment, little is known about the impact of pre-existing malignancy on pathogen-specific immune responses. Here, we sought to characterize the antigen-specific CD8+ T cell response following a bacterial infection in the setting of pre-existing pancreatic adenocarcinoma. Mice with established subcutaneous pancreatic adenocarcinomas were infected with Listeria monocytogenes, and antigen-specific CD8+ T cell responses were compared to those in control mice without cancer. While the kinetics and magnitude of antigen-specific CD8+ T cell expansion and accumulation was comparable between the cancer and non-cancer groups, bacterial antigen-specific CD8+ T cells and total CD4+ and CD8+ T cells in cancer mice exhibited increased expression of the coinhibitory receptors BTLA, PD-1, and 2B4. Furthermore, increased inhibitory receptor expression was associated with reduced IFN-γ and increased IL-2 production by bacterial antigen-specific CD8+ T cells in the cancer group. Taken together, these data suggest that cancer's immune suppressive effects are not limited to the tumor microenvironment, but that pre-existing malignancy induces phenotypic exhaustion in T cells by increasing expression of coinhibitory receptors and may impair pathogen-specific CD8+ T cell functionality and differentiation.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24796533/pdf/?tool=EBI |
| spellingShingle | Rohit Mittal Maylene Wagener Elise R Breed Zhe Liang Benyam P Yoseph Eileen M Burd Alton B Farris Craig M Coopersmith Mandy L Ford Phenotypic T cell exhaustion in a murine model of bacterial infection in the setting of pre-existing malignancy. PLoS ONE |
| title | Phenotypic T cell exhaustion in a murine model of bacterial infection in the setting of pre-existing malignancy. |
| title_full | Phenotypic T cell exhaustion in a murine model of bacterial infection in the setting of pre-existing malignancy. |
| title_fullStr | Phenotypic T cell exhaustion in a murine model of bacterial infection in the setting of pre-existing malignancy. |
| title_full_unstemmed | Phenotypic T cell exhaustion in a murine model of bacterial infection in the setting of pre-existing malignancy. |
| title_short | Phenotypic T cell exhaustion in a murine model of bacterial infection in the setting of pre-existing malignancy. |
| title_sort | phenotypic t cell exhaustion in a murine model of bacterial infection in the setting of pre existing malignancy |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24796533/pdf/?tool=EBI |
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