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Neurology. 2014 Apr 8;82(14):1261-5. doi: 10.1212/WNL.0000000000000290. Epub 2014 Mar 12.

CTL responses to HSP47 associated with the prolonged survival of patients with glioblastomas.

Author information

  • 1From 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.

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.

CONCLUSION:

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.

PMID:
24623841
DOI:
10.1212/WNL.0000000000000290
[PubMed - indexed for MEDLINE]
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