title: CTL responses to HSP47 associated with the prolonged survival of patients with glioblastomas.
abstract: OBJECTIVE
  To define heat shock protein 47 (HSP47) as a novel glioma-associated antigen and to preliminarily assess the association of cytotoxic T lymphocyte (CTL) responses to HSP47 with clinical outcomes in patients with glioblastomas (GBMs).
  
  
  METHODS
  The expression of HSP47 was determined in primary GBM tissues (n = 17) and controlled brain tissues (n = 10) by Western blot. Candidate epitope peptides were predicted using the human leukocyte antigen (HLA) Peptide Binding Predictions Program. The CTL responses to HSP47 were quantified in peripheral blood mononuclear cells from 6 healthy donors and 38 patients (benign tumors = 5, astrocytoma grade II = 7, anaplastic gliomas grade III = 10, GBMs = 16) by stimulation with the mixture of the identified peptides above. Kaplan-Meier survival curves were used to analyze the association between CTL responses and clinical outcomes.
  
  
  RESULTS
  Expression of HSP47 was hardly detectable in controlled brain tissues and increased in GBM tissues (p = 0.018). HSP47(184-192) (KLPEVTKDV) and HSP47(3-11) (LLLLSAFCL) were predicted as the most potent candidate epitope peptides with experimentally confirmed binding affinity to the HLA-A0201 molecule. Seven of 26 patients (26.9%) with malignant gliomas had positive CTL responses. Furthermore, patients with GBM with positive CTL responses to HSP47 experienced a prolonged progress-free survival time (12.6 ± 1.3 vs 8.1 ± 3.2 months, p = 0.01) and overall survival (13.4 ± 1.3 vs 10.4 ± 2.7 months, p = 0.035) than those with negative responses.
  
  
  CONCLUSIONS
  Our data demonstrated that HSP47 is a novel glioma-associated antigen. HSP47-based vaccine will likely confer additional survival benefit to patients with GBM after surgical treatment.
authors.affiliation: From the Department of Neurosurgery (Z.B.W., Y.Y., L.F.Z.), Huashan Hospital, Fudan University, Shanghai; Department of Neurosurgery (Z.B.W., L.C., S.J.L.), First Affiliated Hospital of Wenzhou Medical University, Wenzhou; and Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences (C.Q., A.L.Z., J.X.), Key Laboratory of Medical Molecular Virology of Ministry of Education/Health at Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Zhe Bao
authors.initials: ZB
authors.lastname: Wu
authors.forename: Lin
authors.initials: L
authors.lastname: Cai
authors.forename: Chao
authors.initials: C
authors.lastname: Qiu
authors.forename: An Li
authors.initials: AL
authors.lastname: Zhang
authors.forename: Shao Jian
authors.initials: SJ
authors.lastname: Lin
authors.forename: Yu
authors.initials: Y
authors.lastname: Yao
authors.forename: Jianqing
authors.initials: J
authors.lastname: Xu
authors.forename: Liang Fu
authors.initials: LF
authors.lastname: Zhou
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000276:immunology / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D002648:Child; D005260:Female; D005909:Glioblastoma / Q000276:immunology / Q000378:metabolism* / Q000401:mortality*; D050958:HSP47 Heat-Shock Proteins / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism*
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D050958:HSP47 Heat-Shock Proteins; C494660:SERPINH1 protein, human