CD8+ T cells specific for the androgen receptor are common in patients with prostate cancer and are able to lyse prostate tumor cells

Cancer Immunol Immunother. 2011 Jun;60(6):781-92. doi: 10.1007/s00262-011-0987-5. Epub 2011 Feb 25.


The androgen receptor (AR) is a hormone receptor that plays a critical role in prostate cancer, and depletion of its ligand has long been the cornerstone of treatment for metastatic disease. Here, we evaluate the AR ligand-binding domain (LBD) as an immunological target, seeking to identify HLA-A2-restricted epitopes recognized by T cells in prostate cancer patients. Ten AR LBD-derived, HLA-A2-binding peptides were identified and ranked with respect to HLA-A2 affinity and were used to culture peptide-specific T cells from HLA-A2+ prostate cancer patients. These T-cell cultures identified peptide-specific T cells specific for all ten peptides in at least one patient, and T cells specific for peptides AR805 and AR811 were detected in over half of patients. Peptide-specific CD8+ T-cell clones were then isolated and characterized for prostate cancer cytotoxicity and cytokine expression, identifying that AR805 and AR811 CD8+ T-cell clones could lyse prostate cancer cells in an HLA-A2-restricted fashion, but only AR811 CTL had polyfunctional cytokine expression. Epitopes were confirmed using immunization studies in HLA-A2 transgenic mice, in which the AR LBD is an autologous antigen with an identical protein sequence, which showed that mice immunized with AR811 developed peptide-specific CTL that lyse HLA-A2+ prostate cancer cells. These data show that AR805 and AR811 are HLA-A2-restricted epitopes for which CTL can be commonly detected in prostate cancer patients. Moreover, CTL responses specific for AR811 can be elicited by direct immunization of A2/DR1 mice. These findings suggest that it may be possible to elicit an anti-prostate tumor immune response by augmenting CTL populations using AR LBD-based vaccines.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Line, Tumor
  • Cytokines / biosynthesis
  • Cytokines / immunology
  • Epitopes, T-Lymphocyte / immunology*
  • HLA-A2 Antigen / biosynthesis
  • HLA-A2 Antigen / genetics
  • HLA-A2 Antigen / immunology
  • HLA-DR1 Antigen / genetics
  • HLA-DR1 Antigen / immunology
  • Humans
  • Ligands
  • Male
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Oligopeptides / immunology
  • Oligopeptides / pharmacology
  • Prostatic Neoplasms / immunology*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / therapy
  • Protein Structure, Tertiary
  • Receptors, Androgen / immunology*
  • Receptors, Androgen / metabolism
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism


  • Cytokines
  • Epitopes, T-Lymphocyte
  • HLA-A2 Antigen
  • HLA-DR1 Antigen
  • Ligands
  • Oligopeptides
  • Receptors, Androgen