A cancer vaccine induces expansion of NY-ESO-1-specific regulatory T cells in patients with advanced melanoma.

Cancer vaccines are designed to expand tumor antigen-specific T cells with effector function. However, they may also inadvertently expand regulatory T cells (Treg), which could seriously hamper clinical efficacy. To address this possibility, we developed a novel assay to detect antigen-specific Treg...

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Autores principales:	Lisa M Ebert, Sarah E MacRaild, Damien Zanker, Ian D Davis, Jonathan Cebon, Weisan Chen
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/393a4d7a5c9e48a1a1f5bf4737d14e15
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spelling	oai:doaj.org-article:393a4d7a5c9e48a1a1f5bf4737d14e152021-11-18T08:10:49ZA cancer vaccine induces expansion of NY-ESO-1-specific regulatory T cells in patients with advanced melanoma.1932-620310.1371/journal.pone.0048424https://doaj.org/article/393a4d7a5c9e48a1a1f5bf4737d14e152012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23110239/?tool=EBIhttps://doaj.org/toc/1932-6203Cancer vaccines are designed to expand tumor antigen-specific T cells with effector function. However, they may also inadvertently expand regulatory T cells (Treg), which could seriously hamper clinical efficacy. To address this possibility, we developed a novel assay to detect antigen-specific Treg based on down-regulation of surface CD3 following TCR engagement, and used this approach to screen for Treg specific to the NY-ESO-1 tumor antigen in melanoma patients treated with the NY-ESO-1/ISCOMATRIX™ cancer vaccine. All patients tested had Treg (CD25(bright) FoxP3(+) CD127(neg)) specific for at least one NY-ESO-1 epitope in the blood. Strikingly, comparison with pre-treatment samples revealed that many of these responses were induced or boosted by vaccination. The most frequently detected response was toward the HLA-DP4-restricted NY-ESO-1(157-170) epitope, which is also recognized by effector T cells. Notably, functional Treg specific for an HLA-DR-restricted epitope within the NY-ESO-1(115-132) peptide were also identified at high frequency in tumor tissue, suggesting that NY-ESO-1-specific Treg may suppress local anti-tumor immune responses. Together, our data provide compelling evidence for the ability of a cancer vaccine to expand tumor antigen-specific Treg in the setting of advanced cancer, a finding which should be given serious consideration in the design of future cancer vaccine clinical trials.Lisa M EbertSarah E MacRaildDamien ZankerIan D DavisJonathan CebonWeisan ChenPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 10, p e48424 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lisa M Ebert Sarah E MacRaild Damien Zanker Ian D Davis Jonathan Cebon Weisan Chen A cancer vaccine induces expansion of NY-ESO-1-specific regulatory T cells in patients with advanced melanoma.
description	Cancer vaccines are designed to expand tumor antigen-specific T cells with effector function. However, they may also inadvertently expand regulatory T cells (Treg), which could seriously hamper clinical efficacy. To address this possibility, we developed a novel assay to detect antigen-specific Treg based on down-regulation of surface CD3 following TCR engagement, and used this approach to screen for Treg specific to the NY-ESO-1 tumor antigen in melanoma patients treated with the NY-ESO-1/ISCOMATRIX™ cancer vaccine. All patients tested had Treg (CD25(bright) FoxP3(+) CD127(neg)) specific for at least one NY-ESO-1 epitope in the blood. Strikingly, comparison with pre-treatment samples revealed that many of these responses were induced or boosted by vaccination. The most frequently detected response was toward the HLA-DP4-restricted NY-ESO-1(157-170) epitope, which is also recognized by effector T cells. Notably, functional Treg specific for an HLA-DR-restricted epitope within the NY-ESO-1(115-132) peptide were also identified at high frequency in tumor tissue, suggesting that NY-ESO-1-specific Treg may suppress local anti-tumor immune responses. Together, our data provide compelling evidence for the ability of a cancer vaccine to expand tumor antigen-specific Treg in the setting of advanced cancer, a finding which should be given serious consideration in the design of future cancer vaccine clinical trials.
format	article
author	Lisa M Ebert Sarah E MacRaild Damien Zanker Ian D Davis Jonathan Cebon Weisan Chen
author_facet	Lisa M Ebert Sarah E MacRaild Damien Zanker Ian D Davis Jonathan Cebon Weisan Chen
author_sort	Lisa M Ebert
title	A cancer vaccine induces expansion of NY-ESO-1-specific regulatory T cells in patients with advanced melanoma.
title_short	A cancer vaccine induces expansion of NY-ESO-1-specific regulatory T cells in patients with advanced melanoma.
title_full	A cancer vaccine induces expansion of NY-ESO-1-specific regulatory T cells in patients with advanced melanoma.
title_fullStr	A cancer vaccine induces expansion of NY-ESO-1-specific regulatory T cells in patients with advanced melanoma.
title_full_unstemmed	A cancer vaccine induces expansion of NY-ESO-1-specific regulatory T cells in patients with advanced melanoma.
title_sort	cancer vaccine induces expansion of ny-eso-1-specific regulatory t cells in patients with advanced melanoma.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/393a4d7a5c9e48a1a1f5bf4737d14e15
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A cancer vaccine induces expansion of NY-ESO-1-specific regulatory T cells in patients with advanced melanoma.

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