Th1/Th2 CD4+ T cell responses against NY-ESO-1 in HLA-DPB1*0401/0402 patients with epithelial ovarian cancer

Cancer Immun. 2004 Nov 3;4:12.

Abstract

The NY-ESO-1 antigen is expressed in a significant proportion of patients with epithelial ovarian cancer (EOC) and appears to be an ideal target for immunotherapy. In order to elucidate the nature of the HLA-DPB1*0401/0402 (DP4+)-restricted CD4+ immune response in patients with NY-ESO-1-expressing EOC, peripheral blood CD4+ T cells from HLA-DP4+ patients were stimulated with the NY-ESO-1 epitope 157-170 and tested for the release of type 1 (IFN-gamma) and type 2 (IL-5) cytokines in enzyme-linked immunospot assays. Of 14 DP4+ EOC patients who tested seronegative for NY-ESO-1, 3 patients had a detectable CD4+ T cell response to NY-ESO-1 epitope 157-170 by IFN-gamma ELISPOT assay. Six of 10 DP4+ EOC patients with serum antibodies to NY-ESO-1 had CD4+ T cell responses to NY-ESO-1 epitope 157-170 by IFN-gamma assay. Six patients had mixed Th1/Th2 CD4+ T cell responses to NY-ESO-1 epitope 157-170 regardless of their antibody response to NY-ESO-1. Four EOC patients had Th1 cells expressing IFN-gamma, but not IL-5. This suggests that the NY-ESO-1 epitope 157-170 stimulates both Th1 and Th2 type CD4+ T cell responses in EOC patients. These data suggest the NY-ESO-1 epitope 157-170 has a key role in the induction of cellular and humoral immune responses against NY-ESO-1-expressing EOC tumors. Our study supports the relevance of cancer vaccine trials with the NY-ESO-1 epitope 157-170 in HLA-DP4+ EOC patients with NY-ESO-1-expressing tumors and strategies to improve Th1-dominated tumor-reactive CD4+ T cell bias.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Neoplasm / blood
  • Antigens, Neoplasm / immunology*
  • Antigens, Neoplasm / metabolism
  • Carcinoma / diagnosis
  • Carcinoma / immunology*
  • Female
  • HLA-DP Antigens / analysis*
  • HLA-DP beta-Chains
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-5 / metabolism
  • Membrane Proteins / immunology*
  • Membrane Proteins / metabolism
  • Middle Aged
  • Ovarian Neoplasms / diagnosis
  • Ovarian Neoplasms / immunology*
  • Peptides / immunology
  • Th1 Cells / immunology*
  • Th2 Cells / immunology*

Substances

  • Antibodies, Neoplasm
  • Antigens, Neoplasm
  • CTAG1B protein, human
  • HLA-DP Antigens
  • HLA-DP beta-Chains
  • HLA-DPB1 antigen
  • HLA-DPB1*04:01 antigen
  • HLA-DPB1*04:02 antigen
  • HLA-DPw4 antigen
  • Interleukin-5
  • Membrane Proteins
  • Peptides
  • Interferon-gamma