PMID- 24623841
OWN - NLM
STAT- MEDLINE
DCOM- 20140618
LR  - 20151119
IS  - 1526-632X (Electronic)
IS  - 0028-3878 (Linking)
VI  - 82
IP  - 14
DP  - 2014 Apr 8
TI  - CTL responses to HSP47 associated with the prolonged survival of patients with 
      glioblastomas.
PG  - 1261-5
LID - 10.1212/WNL.0000000000000290 [doi]
AB  - 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.
FAU - Wu, Zhe Bao
AU  - Wu ZB
AD  - From 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.
FAU - Cai, Lin
AU  - Cai L
FAU - Qiu, Chao
AU  - Qiu C
FAU - Zhang, An Li
AU  - Zhang AL
FAU - Lin, Shao Jian
AU  - Lin SJ
FAU - Yao, Yu
AU  - Yao Y
FAU - Xu, Jianqing
AU  - Xu J
FAU - Zhou, Liang Fu
AU  - Zhou LF
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140312
PL  - United States
TA  - Neurology
JT  - Neurology
JID - 0401060
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (HSP47 Heat-Shock Proteins)
RN  - 0 (SERPINH1 protein, human)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antigens, Neoplasm/immunology/*metabolism
MH  - Biomarkers, Tumor/metabolism
MH  - Brain Neoplasms/immunology/metabolism/*mortality/pathology
MH  - Child
MH  - Female
MH  - Glioblastoma/immunology/*metabolism/*mortality
MH  - HSP47 Heat-Shock Proteins/immunology/*metabolism
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - T-Lymphocytes, Cytotoxic/immunology/*metabolism
EDAT- 2014/03/14 06:00
MHDA- 2014/06/19 06:00
CRDT- 2014/03/14 06:00
PHST- 2014/03/14 06:00 [entrez]
PHST- 2014/03/14 06:00 [pubmed]
PHST- 2014/06/19 06:00 [medline]
AID - WNL.0000000000000290 [pii]
AID - 10.1212/WNL.0000000000000290 [doi]
PST - ppublish
SO  - Neurology. 2014 Apr 8;82(14):1261-5. doi: 10.1212/WNL.0000000000000290. Epub 2014 
      Mar 12.