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

Mingjun Wang, Bingnan Yin, Satoko Matsueda, Lijuan Deng, Ying Li, Wei Zhao, Jia Zou, Qingtian Li, Christopher Loo, Rong Fu Wang, Helen Y. Wang

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

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, SATB1565-574 frequently induced peptide-specific T cell responses in PBMCs from both healthy donors and cancer patients. Importantly, SATB1565-574-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.

Original languageEnglish (US)
Article numbere56730
JournalPLoS ONE
Volume8
Issue number2
DOIs
StatePublished - Feb 21 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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