Mechanisms and effects of loss of human leukocyte antigen class II expression in immune-privileged site-associated B-cell lymphoma

Marije Booman, Jenny Douwes, Annuska M Glas, Sietske A Riemersma, Ekaterina S Jordanova, Klaas Kok, Andreas Rosenwald, Daphne de Jong, Ed Schuuring, Philip M Kluin

Research output: Contribution to journalArticleAcademicpeer-review

68 Citations (Scopus)

Abstract

PURPOSE AND EXPERIMENTAL DESIGN: Loss of human leukocyte antigen (HLA) expression on tumor cells is frequent in diffuse large B-cell lymphoma (DLBCL) arising in immune-privileged sites, such as the testis and central nervous system, and is associated with small homozygous deletions of HLA-DQ/HLA-DR and larger hemizygous deletions of the MHC region. To better understand the significance of down-regulation of HLA class II expression in relation to the homozygous and hemizygous deletions, we analyzed global gene expression patterns in a series of 26 testicular DLBCL after characterization of these deletions.

RESULTS: Low levels of HLA-DR mRNA in whole testicular DLBCL samples were associated with a strong down-regulation of numerous immune-related genes specific for T cells, macrophages, antigen presentation and processing, lymphocyte activation, chemokines and chemokine receptors, and the complement system. The number of CD3+ tumor-infiltrating T cells was also significantly lower in low expressors of HLA-DR mRNA. Interestingly, hemizygous and homozygous deletions in the MHC region did not have any additional effect on global gene expression.

CONCLUSION: In conclusion, we found that loss of HLA class II mRNA expression in testicular DLBCL is associated with a significant change in global gene expression patterns. This effect is independent of the mechanism causing the down-regulation of HLA class II genes in the lymphoma cells.

Original languageEnglish
Pages (from-to)2698-705
Number of pages8
JournalClinical Cancer Research
Volume12
Issue number9
DOIs
Publication statusPublished - 1 May 2006

Keywords

  • Centromere
  • Chromosomes, Human, Pair 6
  • Gene Expression Regulation, Neoplastic
  • HLA-D Antigens
  • Humans
  • In Situ Hybridization, Fluorescence
  • Journal Article
  • Lymph Nodes
  • Lymphoma, B-Cell
  • Lymphoma, Large-Cell, Immunoblastic
  • Major Histocompatibility Complex
  • Male
  • Oligonucleotide Array Sequence Analysis
  • Sequence Deletion
  • Telomere
  • Testis

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