CTL responses to HSP47 associated with the prolonged survival of patients with glioblastomas.
Neurology
; 82(14): 1261-5, 2014 Apr 08.
Article
em En
| MEDLINE
| ID: mdl-24623841
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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Encefálicas
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Linfócitos T Citotóxicos
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Glioblastoma
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Proteínas de Choque Térmico HSP47
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Antígenos de Neoplasias
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Child
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Neurology
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
China