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

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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.
Original languageEnglish
Pages (from-to)1101-1109
JournalAnti-Cancer Agents in Medicinal Chemistry
Volume14
Issue number8
Publication statusPublished - 2014

Subject classification (UKÄ)

  • Pharmacology and Toxicology

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