Identification of special AT-rich sequence binding protein 1 as a novel tumor antigen recognized by CD8+ T cells: implication for cancer immunotherapy

• Published in: PloS one Vol. 8; no. 2; p. e56730
• Main Authors: Wang, Mingjun, Yin, Bingnan, Matsueda, Satoko, Deng, Lijuan, Li, Ying, Zhao, Wei, Zou, Jia, Li, Qingtian, Loo, Christopher, Wang, Rong-Fu, Wang, Helen Y
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 21.02.2013; Public Library of Science (PLoS)
• Subjects: Amino acid sequence; Antigen (tumor-associated); Antigens; Antigens, Neoplasm - genetics; Binding; Bioinformatics; Biology; Biomarkers, Tumor - genetics; Biomarkers, Tumor - immunology; Breast cancer; Cancer; Cancer immunotherapy; Cancer vaccines; Cancer Vaccines - genetics; Cancer Vaccines - immunology; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cell Line, Tumor; Diagnostic systems; Epigenetics; Epitopes; Epitopes - genetics; Epitopes - immunology; Gene expression; Gene Expression Regulation, Neoplastic - immunology; Gene therapy; Genomes; Histocompatibility antigen HLA; Histocompatibility Antigens Class I - genetics; Histocompatibility Antigens Class I - immunology; Humans; Identification; Immune system; Immunology; Immunotherapy; Inflammation; Informatics; Leukocytes; Leukocytes (mononuclear); Lymphocytes; Lymphocytes T; Matrix Attachment Region Binding Proteins - genetics; Matrix Attachment Region Binding Proteins - immunology; Medicine; Melanoma; Metastases; Metastasis; Neoplasms - genetics; Neoplasms - immunology; Neoplasms - therapy; Ovarian cancer; Patients; Peptides; Peptides - genetics; Peptides - immunology; Peripheral blood mononuclear cells; Prostate; Prostate cancer; Proteins; Skin cancer; Stem cells; T cell receptors; Tumor cells; Vaccines; United States > US; Texas
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0056730

A large number of human tumor-associated antigens that are recognized by CD8(+) T cells in a human leukocyte antigen class I (HLA-I)-restricted fashion have been identified. Special AT-rich sequence binding protein 1 (SATB1) is highly expressed in many types of human cancers as part of their neoplastic phenotype, and up-regulation of SATB1 expression is essential for tumor survival and metastasis, thus this protein may serve as a rational target for cancer vaccines. Twelve SATB1-derived peptides were predicted by an immuno-informatics approach based on the HLA-A*02 binding motif. These peptides were examined for their ability to induce peptide-specific T cell responses in peripheral blood mononuclear cells (PBMCs) obtained from HLA-A*02(+) healthy donors and/or HLA-A*02(+) cancer patients. The recognition of HLA-A*02(+) SATB1-expressing cancer cells was also tested. Among the twelve SATB1-derived peptides, SATB1(565-574) frequently induced peptide-specific T cell responses in PBMCs from both healthy donors and cancer patients. Importantly, SATB1(565-574)-specific T cells recognized and killed HLA-A*02(+) SATB1(+) cancer cells in an HLA-I-restricted manner. We have identified a novel HLA-A*02-restricted SATB1-derived peptide epitope recognized by CD8(+) T cells, which, in turn, recognizes and kills HLA-A*02(+) SATB1(+) tumor cells. The SATB1-derived epitope identified may be used as a diagnostic marker as well as an immune target for development of cancer vaccines.