Regulatory T-cell response and tumor vaccine-induced cytotoxic T lymphocytes in human melanoma

Hum Immunol. 2004 Aug;65(8):794-802. doi: 10.1016/j.humimm.2004.05.012.


A role of CD4(+) cells in the regulation of immune responses has steadily gained renewed recognition. The understanding of these T-regulatory (T-reg) cells in the generation of antitumor cytolytic T lymphocyte (CTL) response is therefore important. It has been shown that immunization with specific peptides, DNA, or tumor lysate-based vaccines can induce CTL responses in vivo. We have immunized melanoma patients with major histocompatibility complex (MHC) class I restricted peptide- or melanoma tumor lysate-loaded antigen-presenting cell (APC)-based vaccines and have monitored the generation of CTL responses and T-reg cell responses, if any. Using tetramer staining and limiting dilution analyses as monitors of CTL responses, we found significant increases in the number of antigen-specific CTL in circulation after vaccination with the MART-1(27-35) peptide (AAGIGILTV)-pulsed autologous APC, the MAGE-1(161-169) peptide (EADPTGHSY)-pulsed APC, or with autologous tumor lysate-pulsed APC. The antigen-specific CTL reached the peak expansion by day 7 and then declined to the prevaccine levels by day 28. The decline in the CTL response was associated by a concomitant expansion of CD4(+) CD25(+)T cells. Analysis of postvaccine peripheral blood lymphocytes (PBL) from patients showed an increased amount of interleukin (IL)-10 secretion on in vitro stimulation with IL-2 after successive vaccination. Triple color flow cytometric analyses revealed cytoplasmic IL-10 in the CD4(+)CD25(+) T-cell fraction and the number of CD4(+)CD25(+) IL-10(+) T cells were found to increase significantly in postvaccine PBL. These observations have implications in tumor antigen and APC/dendritic cell (DC)-based cancer vaccine strategies.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigen-Presenting Cells / immunology
  • Antigens, Neoplasm
  • CD4-Positive T-Lymphocytes / immunology*
  • Cancer Vaccines / immunology*
  • HLA-A Antigens / chemistry
  • HLA-A Antigens / immunology
  • HLA-A2 Antigen
  • Humans
  • Interleukin-10 / analysis
  • Interleukin-10 / immunology
  • Isoantigens / immunology
  • Lymphocytes, Tumor-Infiltrating / drug effects
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Melanoma / drug therapy
  • Melanoma / immunology*
  • Melanoma-Specific Antigens
  • Neoplasm Proteins / immunology
  • Peptide Fragments / immunology
  • Peptides / immunology
  • T-Lymphocytes, Cytotoxic / immunology*


  • Antigens, Neoplasm
  • Cancer Vaccines
  • HLA-A Antigens
  • HLA-A*02:01 antigen
  • HLA-A2 Antigen
  • Isoantigens
  • MAGEA1 protein, human
  • MART-1 antigen (27-35), Leu(28)-beta-HIle(30)-
  • Melanoma-Specific Antigens
  • Neoplasm Proteins
  • Peptide Fragments
  • Peptides
  • Interleukin-10