New peptides of the polycomb group protein enhancer of zeste homolog 2 with the potential to induce cancer-reactive cytotoxic T lymphocytes in human leukocyte antigen-A2+ prostate cancer patients.
The polycomb group protein enhancer of zeste homolog 2 (EZH2) is linked to aggressive prostate cancer and could be an appropriate target in specific immunotherapy. In this study, we attempted to identify EZH2-derived peptides that have the potential to generate cancer-reactive cytotoxic T lymphocytes (CTLs) in human leukocyte antigen (HLA)-A2+ prostate cancer patients. Twelve EZH2-derived peptides were prepared based on the HLA-A2 binding motif. These peptide candidates were screened first by their ability to be recognized by immunoglobulin G (IgG), and then by their ability to induce peptide-specific cytotoxic T lymphocytes (CTLs). As a result, five EZH2 peptides recognized by IgG (EZH2 120-128, EZH2 165-174, EZH2 569-577, EZH2 665-674, and EZH2 699-708) were frequently detected in the plasma of prostate cancer patients. Among them, the EZH2 120-128 and EZH2 165-174 peptides effectively induced HLA-A2-restricted and cancer-reactive CTLs from prostate cancer patients. The cytotoxicity was mainly dependent on EZH2 peptide-specific and HLA-A2-restricted CD8+ T cells. These results indicate that these EZH2 120-128 and EZH2 165-174 peptides could be promising candidates in peptide-based immunotherapy for HLA-A2+ prostate cancer patients.
Itoh
Yukoh
Y
Department of Immunology, Kurume University School of Medicine, Fukuoka, Japan.
Komohara
Yoshihiro
Y
Komatsu
Nobukazu
N
Minami
Takafumi
T
Saito
Koujiro
K
Noguchi
Masanori
M
Itoh
Kyogo
K
Harada
Mamoru
M
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003080:Cold Temperature; D004268:DNA-Binding Proteins / Q000276:immunology*; D000071221:Enhancer of Zeste Homolog 2 Protein; D015789:HLA-A2 Antigen / Q000276:immunology*; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000276:immunology; D063151:Polycomb Repressive Complex 2; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000503:physiopathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014157:Transcription Factors / Q000276:immunology*
D004268:DNA-Binding Proteins; D015789:HLA-A2 Antigen; D010446:Peptide Fragments; D014157:Transcription Factors; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2