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Journal of Immunology Research
Volume 2014, Article ID 131494, 12 pages
http://dx.doi.org/10.1155/2014/131494
Research Article

Glioma-Associated Antigen HEATR1 Induces Functional Cytotoxic T Lymphocytes in Patients with Glioma

1Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China
2Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
3Department of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
4Key Laboratory of Medical Molecular Virology of Ministry of Education/Health at Shanghai Medical College, Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Fudan University, Jinshan District, Shanghai 200040, China
5Department of Immunology and Biotherapy Research Center, Shanghai Medical College, Fudan University, Shanghai 200040, China

Received 8 March 2014; Revised 17 May 2014; Accepted 16 June 2014; Published 9 July 2014

Academic Editor: Bin Zhang

Copyright © 2014 Zhe Bao Wu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

A2B5+ glioblastoma (GBM) cells have glioma stem-like cell (GSC) properties that are crucial to chemotherapy resistance and GBM relapse. T-cell-based antigens derived from A2B5+ GBM cells provide important information for immunotherapy. Here, we show that HEAT repeat containing 1 (HEATR1) expression in GBM tissues was significantly higher than that in control brain tissues. Furthermore, HEATR1 expression in A2B5+ U87 cells was higher than that in A2B5−U87 cells ( ). Six peptides of HEATR1 presented by HLA-A 02 were selected for testing of their ability to induce T-cell responses in patients with GBM. When peripheral blood mononuclear cells from healthy donors ( ) and patients with glioma ( ) were stimulated with the peptide mixture, eight patients with malignant gliomas had positive reactivity with a significantly increased number of responding T-cells. The peptides HEATR1682–690, HEATR11126–1134, and HEATR1757–765 had high affinity for binding to HLA-A 02:01 and a strong capacity to induce CTL response. CTLs against HEATR1 peptides were capable of recognizing and lysing GBM cells and GSCs. These data are the first to demonstrate that HEATR1 could induce specific CTL responses targeting both GBM cells and GSCs, implicating that HEATR1 peptide-based immunotherapy could be a novel promising strategy for treating patients with GBM.