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

PLoS One. 2012;7(10):e48424. doi: 10.1371/journal.pone.0048424. Epub 2012 Oct 26.

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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cancer Vaccines / therapeutic use*
  • Cells, Cultured
  • Epitopes / immunology
  • Flow Cytometry
  • Humans
  • Leukocytes, Mononuclear / metabolism
  • Melanoma / immunology*
  • Melanoma / pathology
  • Melanoma / therapy*
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • Cancer Vaccines
  • Epitopes

Grant support

This work was supported by Cancer Council Victoria grants to LE (603103, 433626), a National Health and Medical Research Council (NHMRC) project grant to WC (433608) and Operational Infrastructure Support of the Victorian State Government. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.