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

Zhe Bao Wu, Lin Cai, Chao Qiu, An Li Zhang, Shao Jian Lin, Yu Yao, Jianqing Xu, Liang Fu Zhou

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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 5 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). HSP47184-192 (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.

Original languageEnglish (US)
Pages (from-to)1261-1265
Number of pages5
JournalNeurology
Volume82
Issue number14
DOIs
StatePublished - Apr 8 2014
Externally publishedYes

ASJC Scopus subject areas

  • Clinical Neurology

Fingerprint

Dive into the research topics of 'CTL responses to HSP47 associated with the prolonged survival of patients with glioblastomas'. Together they form a unique fingerprint.

Cite this