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

Lisa Ebert, Sarah MacRaild, Damien Zanker, Ian Davis, Jonathan Cebon, Weisan Chen

Research output: Contribution to journalArticleResearchpeer-review

44 Citations (Scopus)

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/ISCOMATRIXTM cancer vaccine. All patients tested had Treg (CD25bright FoxP3+ CD127neg) 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-1157-170 epitope, which is also recognized by effector T cells. Notably, functional Treg specific for an HLADR- restricted epitope within the NY-ESO-1115-132 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.
Original languageEnglish
Article numbere48424
Number of pages10
JournalPLoS ONE
Volume7
Issue number10
DOIs
Publication statusPublished - 2012

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