Anti-Cancer Agents in Medicinal Chemistry

(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Michelle Prudhomme  
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex
France

Back

Tapasin and Human Leukocyte Antigen Class I Dysregulation Correlates with Survival in Glioblastoma Multiforme

Author(s): Camilla Thuring, Linda Geironson, Kajsa Paulsson.

Graphical Abstract:


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.

Keywords: Brain tumor, CD8, glioblastoma multiforme, HLA-I, MHC-I, tapasin.

Order Reprints Order Eprints Rights & PermissionsPrintExport

Article Details

VOLUME: 14
ISSUE: 8
Page: [1101 - 1109]
Pages: 9
DOI: 10.2174/1871520614666140825110402
Price: $58