| RRC ID |
18593
|
| Author |
Ohue Y, Eikawa S, Okazaki N, Mizote Y, Isobe M, Uenaka A, Fukuda M, Old LJ, Oka M, Nakayama E.
|
| Title |
Spontaneous antibody, and CD4 and CD8 T-cell responses against XAGE-1b (GAGED2a) in non-small cell lung cancer patients.
|
| Journal |
Int J Cancer
|
| Abstract |
The spontaneous immune responses against XAGE-1b (GAGED2a) were analyzed in non-small cell lung cancer (NSCLC) patients. An antibody response against XAGE-1b (GAGED2a) was observed in 10% (20/200) of NSCLC patients and in 19% (13/69) of stage IIIB/IV lung adenocarcinoma patients. A CD4 T-cell response was detected in 88% (14/16) and a CD8 T-cell response in 67% (6/9) in the XAGE-1b (GAGED2a) antibody-positive patients examined. Frequent antibody responses and CD4 and CD8 T-cell responses in XAGE-1b (GAGED2a) antibody-positive patients indicate the strong immunogenicity of the XAGE-1b (GAGED2a) antigen in NSCLC patients. We established T-cell clones from PBMCs of antibody-positive patients and determined the DRB1*04:05-restricted XAGE-1b (GAGED2a) 18-31 peptide (14-mer) as a CD4 T cell epitope and the A*02:06-restricted XAGE-1b (GAGED2a) 21-29 peptide (9-mer) as a CD8 T cell epitope. As for peptide recognition, CD4 and CD8 T-cell clones responded to naturally processed antigen. The CD4 T-cell clone recognized DCs pulsed with the synthetic protein or a lysate from XAGE-1b-transfected 293T cells. The CD8 T-cell clone showed cytotoxicity against a tumor expressing XAGE-1b (GAGED2a) and the appropriate HLA class I allele. These findings establish XAGE-1b (GAGED2a) as a promising target for a lung cancer vaccine.
|
| Volume |
131(5)
|
| Pages |
E649-58
|
| Published |
2012-9-1
|
| DOI |
10.1002/ijc.27359
|
| PMID |
22109656
|
| MeSH |
Adenocarcinoma / genetics
Adenocarcinoma / immunology
Adenocarcinoma / metabolism
Antibodies, Neoplasm / blood*
Antibodies, Neoplasm / immunology
Antigens, Neoplasm / genetics
Antigens, Neoplasm / immunology*
Antigens, Neoplasm / metabolism
Apoptosis
Blotting, Western
CD4-Positive T-Lymphocytes / immunology*
CD4-Positive T-Lymphocytes / metabolism
CD4-Positive T-Lymphocytes / pathology
CD8-Positive T-Lymphocytes / immunology*
CD8-Positive T-Lymphocytes / metabolism
CD8-Positive T-Lymphocytes / pathology
Carcinoma, Large Cell / genetics
Carcinoma, Large Cell / immunology
Carcinoma, Large Cell / metabolism
Carcinoma, Non-Small-Cell Lung / genetics
Carcinoma, Non-Small-Cell Lung / immunology*
Carcinoma, Non-Small-Cell Lung / metabolism
Carcinoma, Squamous Cell / genetics
Carcinoma, Squamous Cell / immunology
Carcinoma, Squamous Cell / metabolism
Case-Control Studies
Cell Proliferation
Dendritic Cells / immunology
Dendritic Cells / metabolism
Dendritic Cells / pathology
Enzyme-Linked Immunosorbent Assay
Epitopes, T-Lymphocyte / immunology
Epitopes, T-Lymphocyte / metabolism
Humans
Interferon-gamma / metabolism
Lung / immunology
Lung / metabolism
Lung Neoplasms / genetics
Lung Neoplasms / immunology*
Lung Neoplasms / metabolism
Neoplasm Staging
Peptide Fragments / immunology
Prognosis
RNA, Messenger / genetics
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Tumor Cells, Cultured
|
| IF |
5.145
|
| Times Cited |
25
|
|
WOS Category
|
ONCOLOGY
|
| Resource |
| Human and Animal Cells |
293T(RCB2202)
RERF-LC-AI(RCB0444) |
