Identification of Special AT-Rich Sequence Binding Protein 1 as a Novel Tumor Antigen Recognized by CD8+ T Cells: Implication for Cancer Immunotherapy

Background 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. Methodology/Principal Findings 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. Conclusions/Significance 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.