Please use this identifier to cite or link to this item:
|Scopus||Web of Science®||Altmetric|
|Title:||A cancer vaccine induces expansion of NY-ESO-1-specific regulatory T cells in patients with advanced melanoma|
|Citation:||PLoS ONE, 2012; 7(10):e48424-1-e48424-10|
|Publisher:||Public Library Science|
|Lisa M. Ebert, Sarah E. MacRaild, Damien Zanker, Ian D. Davis, Jonathan Cebon, Weisan Chen|
|Abstract:||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.|
|Keywords:||Leukocytes, Mononuclear; Cells, Cultured; Humans; Melanoma; Cancer Vaccines; Epitopes; Flow Cytometry; T-Lymphocytes, Regulatory|
|Rights:||© 2012 Ebert et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.|
|Appears in Collections:||Medicine publications|
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.