Th1/Th2 CD4+ T cell responses against NY-ESO-1 in HLA-DPB1*0401/0402 patients with epithelial ovarian cancer.
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.
Qian
Feng
F
Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Gnjatic
Sacha
S
Jäger
Elke
E
Santiago
Darren
D
Jungbluth
Achim
A
Grande
Cathy
C
Schneider
Sally
S
Keitz
Bernadette
B
Driscoll
Deborah
D
Ritter
Gerd
G
Lele
Shashikant
S
Sood
Ashwani
A
Old
Lloyd J
LJ
Odunsi
Kunle
K
D000328:Adult; D000368:Aged; D000912:Antibodies, Neoplasm / Q000097:blood; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D002277:Carcinoma / Q000175:diagnosis / Q000276:immunology*; D005260:Female; D006682:HLA-DP Antigens / Q000032:analysis*; D059868:HLA-DP beta-Chains; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008565:Membrane Proteins / Q000276:immunology* / Q000378:metabolism; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen; C505113:HLA-DPB1*04:01 antigen; C505114:HLA-DPB1*04:02 antigen; C056284:HLA-DPw4 antigen; D015848:Interleukin-5; D008565:Membrane Proteins; D010455:Peptides; D007371:Interferon-gamma