CD4+CD25+FOXP3+ regulatory T cells suppress anti-tumor immune responses in patients with colorectal cancer.

<h4>Background</h4>A wealth of evidence obtained using mouse models indicates that CD4(+)CD25(+)FOXP3(+) regulatory T cells (Treg) maintain peripheral tolerance to self-antigens and also inhibit anti-tumor immune responses. To date there is limited information about CD4(+) T cell respons...

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Main Authors: Sarah L Clarke, Gareth J Betts, Andrea Plant, Kate L Wright, Tariq M El-Shanawany, Richard Harrop, Jared Torkington, Brian I Rees, Geraint T Williams, Awen M Gallimore, Andrew J Godkin
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2006-12-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0000129&type=printable
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author Sarah L Clarke
Gareth J Betts
Andrea Plant
Kate L Wright
Tariq M El-Shanawany
Richard Harrop
Jared Torkington
Brian I Rees
Geraint T Williams
Awen M Gallimore
Andrew J Godkin
author_facet Sarah L Clarke
Gareth J Betts
Andrea Plant
Kate L Wright
Tariq M El-Shanawany
Richard Harrop
Jared Torkington
Brian I Rees
Geraint T Williams
Awen M Gallimore
Andrew J Godkin
author_sort Sarah L Clarke
collection DOAJ
description <h4>Background</h4>A wealth of evidence obtained using mouse models indicates that CD4(+)CD25(+)FOXP3(+) regulatory T cells (Treg) maintain peripheral tolerance to self-antigens and also inhibit anti-tumor immune responses. To date there is limited information about CD4(+) T cell responses in patients with colorectal cancer (CRC). We set out to measure T cell responses to a tumor-associated antigen and examine whether Treg impinge on those anti-tumor immune responses in CRC patients.<h4>Methodology and principal findings</h4>Treg were identified and characterized as CD4(+)CD25(+)FOXP3(+) using flow cytometry. An increased frequency of Treg was demonstrated in both peripheral blood and mesenteric lymph nodes of patients with colorectal cancer (CRC) compared with either healthy controls or patients with inflammatory bowel disease (IBD). Depletion of Treg from peripheral blood mononuclear cells (PBMC) of CRC patients unmasked CD4(+) T cell responses, as observed by IFNgamma release, to the tumor associated antigen 5T4, whereas no effect was observed in a healthy age-matched control group.<h4>Conclusions/significance</h4>Collectively, these data demonstrate that Treg capable of inhibiting tumor associated antigen-specific immune responses are enriched in patients with CRC. These results support a rationale for manipulating Treg to enhance cancer immunotherapy.
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spelling doaj-art-4895a4b8551a4cf1b3dcf51118aa6cb22025-08-20T02:17:28ZengPublic Library of Science (PLoS)PLoS ONE1932-62032006-12-011e12910.1371/journal.pone.0000129CD4+CD25+FOXP3+ regulatory T cells suppress anti-tumor immune responses in patients with colorectal cancer.Sarah L ClarkeGareth J BettsAndrea PlantKate L WrightTariq M El-ShanawanyRichard HarropJared TorkingtonBrian I ReesGeraint T WilliamsAwen M GallimoreAndrew J Godkin<h4>Background</h4>A wealth of evidence obtained using mouse models indicates that CD4(+)CD25(+)FOXP3(+) regulatory T cells (Treg) maintain peripheral tolerance to self-antigens and also inhibit anti-tumor immune responses. To date there is limited information about CD4(+) T cell responses in patients with colorectal cancer (CRC). We set out to measure T cell responses to a tumor-associated antigen and examine whether Treg impinge on those anti-tumor immune responses in CRC patients.<h4>Methodology and principal findings</h4>Treg were identified and characterized as CD4(+)CD25(+)FOXP3(+) using flow cytometry. An increased frequency of Treg was demonstrated in both peripheral blood and mesenteric lymph nodes of patients with colorectal cancer (CRC) compared with either healthy controls or patients with inflammatory bowel disease (IBD). Depletion of Treg from peripheral blood mononuclear cells (PBMC) of CRC patients unmasked CD4(+) T cell responses, as observed by IFNgamma release, to the tumor associated antigen 5T4, whereas no effect was observed in a healthy age-matched control group.<h4>Conclusions/significance</h4>Collectively, these data demonstrate that Treg capable of inhibiting tumor associated antigen-specific immune responses are enriched in patients with CRC. These results support a rationale for manipulating Treg to enhance cancer immunotherapy.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0000129&type=printable
spellingShingle Sarah L Clarke
Gareth J Betts
Andrea Plant
Kate L Wright
Tariq M El-Shanawany
Richard Harrop
Jared Torkington
Brian I Rees
Geraint T Williams
Awen M Gallimore
Andrew J Godkin
CD4+CD25+FOXP3+ regulatory T cells suppress anti-tumor immune responses in patients with colorectal cancer.
PLoS ONE
title CD4+CD25+FOXP3+ regulatory T cells suppress anti-tumor immune responses in patients with colorectal cancer.
title_full CD4+CD25+FOXP3+ regulatory T cells suppress anti-tumor immune responses in patients with colorectal cancer.
title_fullStr CD4+CD25+FOXP3+ regulatory T cells suppress anti-tumor immune responses in patients with colorectal cancer.
title_full_unstemmed CD4+CD25+FOXP3+ regulatory T cells suppress anti-tumor immune responses in patients with colorectal cancer.
title_short CD4+CD25+FOXP3+ regulatory T cells suppress anti-tumor immune responses in patients with colorectal cancer.
title_sort cd4 cd25 foxp3 regulatory t cells suppress anti tumor immune responses in patients with colorectal cancer
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0000129&type=printable
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