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.

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.

• Authors: Zhe Bao Wu, Lin Cai, Chao Qiu, An Li Zhang, Shao Jian Lin, Yu Yao, Jianqing Xu, Liang Fu Zhou
• Journal: Neurology (Neurology) Vol. 82 Issue 14 Pg. 1261-5 (Apr 08 2014) ISSN: 1526-632X [Electronic] United States
• PMID: 24623841 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Biomarkers, Tumor
• HSP47 Heat-Shock Proteins
• SERPINH1 protein, human

Topics

• Adult
• Aged
• Antigens, Neoplasm (immunology, metabolism)
• Biomarkers, Tumor (metabolism)
• Brain Neoplasms (immunology, metabolism, mortality, pathology)
• Child
• Female
• Glioblastoma (immunology, metabolism, mortality)
• HSP47 Heat-Shock Proteins (immunology, metabolism)
• Humans
• Male
• Middle Aged
• T-Lymphocytes, Cytotoxic (immunology, metabolism)