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

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)


Volume 16, 12 Issues, 2016


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Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

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Editor-in-Chief:
Michelle Prudhomme
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex
France


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



Anti-Cancer Agents in Medicinal Chemistry, 14(8): 1101-1109.

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

Affiliation: Immunology, Lund University, BMC D14, 221 84 Lund, Sweden.

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.



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Article Details

Volume: 14
Issue Number: 8
First Page: 1101
Last Page: 1109
Page Count: 9
DOI: 10.2174/1871520614666140825110402
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