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...

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Autores principales:	Rohit Mittal, Maylene Wagener, Elise R Breed, Zhe Liang, Benyam P Yoseph, Eileen M Burd, Alton B Farris, Craig M Coopersmith, Mandy L Ford
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/31e83b4735fe437e86aaef097708f8e5
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spelling	oai:doaj.org-article:31e83b4735fe437e86aaef097708f8e52021-11-18T08:20:53ZPhenotypic T cell exhaustion in a murine model of bacterial infection in the setting of pre-existing malignancy.1932-620310.1371/journal.pone.0093523https://doaj.org/article/31e83b4735fe437e86aaef097708f8e52014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24796533/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203While 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.Rohit MittalMaylene WagenerElise R BreedZhe LiangBenyam P YosephEileen M BurdAlton B FarrisCraig M CoopersmithMandy L FordPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 5, p e93523 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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.
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.
format	article
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
title	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_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_sort	phenotypic t cell exhaustion in a murine model of bacterial infection in the setting of pre-existing malignancy.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/31e83b4735fe437e86aaef097708f8e5
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Phenotypic T cell exhaustion in a murine model of bacterial infection in the setting of pre-existing malignancy.

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