CTL responses to HSP47 associated with the prolonged survival of patients with glioblastomas
CTL responses to HSP47 associated with the prolonged survival of patients with glioblastomas
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CTL 对 HSP47 的反应与胶质母细胞瘤患者的延长生存期相关
DOI：
10.1212/wnl.0000000000000290
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发表时间：
2014-04
期刊：
影响因子：
9.9
通讯作者：
Zhou, Liang Fu
中科院分区：
文献类型：
--
作者：
Lin, Shao Jian;Yao, Yu;Xu, Jianqing;Zhou, Liang Fu
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). HSP47184–192 (KLPEVTKDV) and HSP473–11 (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.
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影响因子：
158.5
作者：
Stupp, R;Mason, WP;Ryan, G
通讯作者：
Ryan, G
DOI：
10.1073/pnas.0603512103
发表时间：
2006-08-29
影响因子：
11.1
作者：
Jin, Kunlin;Wang, Xiaomei;Greenberg, David A.
通讯作者：
Greenberg, David A.
DOI：
10.1016/s1040-1741(08)70253-7
发表时间：
2006
期刊：
Yearbook of Oncology
影响因子：
--
作者：
P. Loehrer
通讯作者：
P. Loehrer
影响因子：
3.8
作者：
Hakamada, T;Funatsuki, K;Imawari, M
通讯作者：
Imawari, M
影响因子：
4.4
作者：
Bredenbeck, A;Losch, FO;Walden, P
通讯作者：
Walden, P