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

doi:10.1371/journal.pone.0056730

Abstract

BackgroundA 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 FindingsTwelve 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/SignificanceWe 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.

Highlights

One of the most promising approaches in cancer therapy relies on harnessing the immune system to eradicate malignant cells [1], the success of which relies largely on the identification of suitable tumor-associated antigens (TAA) for generating effective cancer vaccines
It has been well-established that tumor cells express TAAs that can be recognized by CD8+ T cells in the context of human leukocyte antigen class I (HLA-I) molecules
All protocols were approved by the Institutional Review Board (IRB) at the Baylor College of Medicine prior to commencing studies. 20 mL of peripheral blood was obtained from each person, and peripheral blood mononuclear cells (PBMCs) were isolated by density gradient centrifugation using Lymphoprep (Nycomed Pharma AS; Oslo, Norway)

Summary

Introduction

One of the most promising approaches in cancer therapy relies on harnessing the immune system to eradicate malignant cells [1], the success of which relies largely on the identification of suitable tumor-associated antigens (TAA) for generating effective cancer vaccines. It has been well-established that tumor cells express TAAs that can be recognized by CD8+ T cells in the context of human leukocyte antigen class I (HLA-I) molecules. A large number of TAAs and TAA-derived epitopes have been identified [2,3], with some of these proteins and peptide derivatives already in clinical vaccine trials. 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, this protein may serve as a rational target for cancer vaccines

Objectives

Methods

Results

Conclusion