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Tapasin and human leukocyte antigen class I dysregulation correlates with survival in glioblastoma multiforme.

Thuring, Camilla LU ; Geironson Ulfsson, Linda LU and Paulsson, Kajsa M LU (2014) In Anti-Cancer Agents in Medicinal Chemistry 14(8). p.1101-1109
Abstract
Human leukocyte antigen class I (HLA-I) molecules present antigenic peptides to cytotoxic CD8(+) T cells. Downregulation of peptide:HLA-I complexes is common in tumors and results in tumor immune escape variants. Also molecules involved in the maturation of HLA-I have been demonstrated to be dysregulated in malignant neoplasms. We here set out to investigate the antigen presentation capabilities of a set of 12 glioblastoma multiforme (GBM) tumors based on the expression of HLA-I. Moreover, we analyzed the expression of tapasin, a protein dedicated and essential to HLA-I maturation, as well as the infiltration of CD8+ cells using immunohistochemistry on paraffin-embedded sections. Comparison of different GBMs showed a variation in... (More)
Human leukocyte antigen class I (HLA-I) molecules present antigenic peptides to cytotoxic CD8(+) T cells. Downregulation of peptide:HLA-I complexes is common in tumors and results in tumor immune escape variants. Also molecules involved in the maturation of HLA-I have been demonstrated to be dysregulated in malignant neoplasms. We here set out to investigate the antigen presentation capabilities of a set of 12 glioblastoma multiforme (GBM) tumors based on the expression of HLA-I. Moreover, we analyzed the expression of tapasin, a protein dedicated and essential to HLA-I maturation, as well as the infiltration of CD8+ cells using immunohistochemistry on paraffin-embedded sections. Comparison of different GBMs showed a variation in expression of both HLA-I heavy chain (HC) and tapasin. Interestingly, the expression of tapasin and HLA-I HC correlated significantly (p=0.0002) suggesting tapasin to be a key factor for efficient HLA-I antigen presentation in GBMs. Although no statistically significant correlation between CD8(+) cells and survival was found, probably due to a very low number of infiltrating CD8(+) cells at the time of surgical resection, both tapasin and HLA-I HC levels significantly correlated with survival. We suggest that analysis of expression of tapasin and/or HLA-I may be of value as prognostic tool for GBM patients, especially when considering immunotherapy. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Anti-Cancer Agents in Medicinal Chemistry
volume
14
issue
8
pages
1101 - 1109
publisher
Bentham Science Publishers
external identifiers
  • pmid:25175688
  • wos:000341885400006
  • scopus:84907183762
ISSN
1875-5992
language
English
LU publication?
yes
id
e5dd07c2-617d-4349-b402-2a1c9fe1ac03 (old id 4692792)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25175688?dopt=Abstract
date added to LUP
2014-10-01 11:39:54
date last changed
2017-03-26 03:16:04
@article{e5dd07c2-617d-4349-b402-2a1c9fe1ac03,
  abstract     = {Human leukocyte antigen class I (HLA-I) molecules present antigenic peptides to cytotoxic CD8(+) T cells. Downregulation of peptide:HLA-I complexes is common in tumors and results in tumor immune escape variants. Also molecules involved in the maturation of HLA-I have been demonstrated to be dysregulated in malignant neoplasms. We here set out to investigate the antigen presentation capabilities of a set of 12 glioblastoma multiforme (GBM) tumors based on the expression of HLA-I. Moreover, we analyzed the expression of tapasin, a protein dedicated and essential to HLA-I maturation, as well as the infiltration of CD8+ cells using immunohistochemistry on paraffin-embedded sections. Comparison of different GBMs showed a variation in expression of both HLA-I heavy chain (HC) and tapasin. Interestingly, the expression of tapasin and HLA-I HC correlated significantly (p=0.0002) suggesting tapasin to be a key factor for efficient HLA-I antigen presentation in GBMs. Although no statistically significant correlation between CD8(+) cells and survival was found, probably due to a very low number of infiltrating CD8(+) cells at the time of surgical resection, both tapasin and HLA-I HC levels significantly correlated with survival. We suggest that analysis of expression of tapasin and/or HLA-I may be of value as prognostic tool for GBM patients, especially when considering immunotherapy.},
  author       = {Thuring, Camilla and Geironson Ulfsson, Linda and Paulsson, Kajsa M},
  issn         = {1875-5992},
  language     = {eng},
  number       = {8},
  pages        = {1101--1109},
  publisher    = {Bentham Science Publishers},
  series       = {Anti-Cancer Agents in Medicinal Chemistry},
  title        = {Tapasin and human leukocyte antigen class I dysregulation correlates with survival in glioblastoma multiforme.},
  volume       = {14},
  year         = {2014},
}