Optimal population of FoxP3+ T cells in tumors requires an antigen priming-dependent trafficking receptor switch.

FoxP3(+) T cells populate tumors and regulate anti-tumor immunity. The requirement for optimal population of FoxP3(+) regulatory T cells in tumors remains unclear. We investigated the migration requirement and stability of tumor-associated FoxP3(+) T cells. We found that only memory, but not naïve,...

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Main Authors: Chuanwu Wang, Jee H Lee, Chang H Kim
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3264621?pdf=render
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author Chuanwu Wang
Jee H Lee
Chang H Kim
author_facet Chuanwu Wang
Jee H Lee
Chang H Kim
author_sort Chuanwu Wang
collection DOAJ
description FoxP3(+) T cells populate tumors and regulate anti-tumor immunity. The requirement for optimal population of FoxP3(+) regulatory T cells in tumors remains unclear. We investigated the migration requirement and stability of tumor-associated FoxP3(+) T cells. We found that only memory, but not naïve, FoxP3(+) T cells are highly enriched in tumors. Almost all of the tumor-infiltrating FoxP3(+) T cells express Helios, an antigen associated either with thymus-generated FoxP3(+) T cells or activated T cells in the periphery. The tumor-infiltrating FoxP3(+) T cells largely lack CD62L and CCR7, two trafficking receptors required for T cell migration into secondary lymphoid tissues. Instead, the tumor infiltrating FoxP3(+) T cells highly express memory/tumor-associated CCR8 and CXCR4. Antigen priming is required for induction of this trafficking receptor phenotype in FoxP3(+) T cells and only antigen primed, but not antigen-inexperienced naive, FoxP3(+) T cells can efficiently migrate into tumors. While the migration of FoxP3(+) T cells into tumors was a readily detectable event, generation of induced FoxP3(+) T cells within tumors was unexpectedly inefficient. Genetic marking of current and ex-FoxP3(+) T cells revealed that tumor-infiltrating FoxP3(+) T cells are highly stable and do not readily convert back to FoxP3(-) T cells. Taken together, our results indicate that population of tumors with thymus-generated FoxP3(+) T cells requires an antigen priming-dependent trafficking receptor switch in lymphoid tissues.
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spelling doaj.art-6b54b2353573499c90d569305aec757a2022-12-22T03:11:31ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0171e3079310.1371/journal.pone.0030793Optimal population of FoxP3+ T cells in tumors requires an antigen priming-dependent trafficking receptor switch.Chuanwu WangJee H LeeChang H KimFoxP3(+) T cells populate tumors and regulate anti-tumor immunity. The requirement for optimal population of FoxP3(+) regulatory T cells in tumors remains unclear. We investigated the migration requirement and stability of tumor-associated FoxP3(+) T cells. We found that only memory, but not naïve, FoxP3(+) T cells are highly enriched in tumors. Almost all of the tumor-infiltrating FoxP3(+) T cells express Helios, an antigen associated either with thymus-generated FoxP3(+) T cells or activated T cells in the periphery. The tumor-infiltrating FoxP3(+) T cells largely lack CD62L and CCR7, two trafficking receptors required for T cell migration into secondary lymphoid tissues. Instead, the tumor infiltrating FoxP3(+) T cells highly express memory/tumor-associated CCR8 and CXCR4. Antigen priming is required for induction of this trafficking receptor phenotype in FoxP3(+) T cells and only antigen primed, but not antigen-inexperienced naive, FoxP3(+) T cells can efficiently migrate into tumors. While the migration of FoxP3(+) T cells into tumors was a readily detectable event, generation of induced FoxP3(+) T cells within tumors was unexpectedly inefficient. Genetic marking of current and ex-FoxP3(+) T cells revealed that tumor-infiltrating FoxP3(+) T cells are highly stable and do not readily convert back to FoxP3(-) T cells. Taken together, our results indicate that population of tumors with thymus-generated FoxP3(+) T cells requires an antigen priming-dependent trafficking receptor switch in lymphoid tissues.http://europepmc.org/articles/PMC3264621?pdf=render
spellingShingle Chuanwu Wang
Jee H Lee
Chang H Kim
Optimal population of FoxP3+ T cells in tumors requires an antigen priming-dependent trafficking receptor switch.
PLoS ONE
title Optimal population of FoxP3+ T cells in tumors requires an antigen priming-dependent trafficking receptor switch.
title_full Optimal population of FoxP3+ T cells in tumors requires an antigen priming-dependent trafficking receptor switch.
title_fullStr Optimal population of FoxP3+ T cells in tumors requires an antigen priming-dependent trafficking receptor switch.
title_full_unstemmed Optimal population of FoxP3+ T cells in tumors requires an antigen priming-dependent trafficking receptor switch.
title_short Optimal population of FoxP3+ T cells in tumors requires an antigen priming-dependent trafficking receptor switch.
title_sort optimal population of foxp3 t cells in tumors requires an antigen priming dependent trafficking receptor switch
url http://europepmc.org/articles/PMC3264621?pdf=render
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