title: Glioma-associated antigen HEATR1 induces functional cytotoxic T lymphocytes in patients with glioma.
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 (P = 0.016). 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 (n = 6) and patients with glioma (n = 33) 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 HEATR(1682-690), HEATR(11126-1134), and HEATR(1757-765) 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.
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China ; Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China ; Department of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Zhe Bao
authors.initials: ZB
authors.lastname: Wu
authors.affiliation: Key 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.
authors.forename: Chao
authors.initials: C
authors.lastname: Qiu
authors.affiliation: Key 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.
authors.forename: An Li
authors.initials: AL
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Cai
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Shao Jian
authors.initials: SJ
authors.lastname: Lin
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Qi Sheng
authors.initials: QS
authors.lastname: Tang
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Hua
authors.affiliation: Department of Immunology and Biotherapy Research Center, Shanghai Medical College, Fudan University, Shanghai 200040, China.
authors.forename: Yi Wei
authors.initials: YW
authors.lastname: Chu
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Jian Hong
authors.initials: JH
authors.lastname: Zhu
authors.affiliation: Key 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.
authors.forename: Jianqing
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Liang Fu
authors.initials: LF
authors.lastname: Zhou
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D005910:Glioma / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015234:HLA-A Antigens / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D060787:Neoplasm Grading; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism*; D055815:Young Adult
chemical_list: D018984:Epitopes, T-Lymphocyte; C000597348:HEATR1 protein, human; D015234:HLA-A Antigens; D015778:Minor Histocompatibility Antigens; D010455:Peptides; D016601:RNA-Binding Proteins; D007371:Interferon-gamma