PMID- 16675561 OWN - NLM STAT- MEDLINE DCOM- 20060821 LR - 20201226 IS - 1078-0432 (Print) IS - 1078-0432 (Linking) VI - 12 IP - 9 DP - 2006 May 1 TI - Mechanisms and effects of loss of human leukocyte antigen class II expression in immune-privileged site-associated B-cell lymphoma. PG - 2698-705 AB - 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. FAU - Booman, Marije AU - Booman M AD - Department of Pathology and Laboratory Medicine, University Medical Center Groningen, Groningen, Netherlands. m.booman@path.umcg.nl FAU - Douwes, Jenny AU - Douwes J FAU - Glas, Annuska M AU - Glas AM FAU - Riemersma, Sietske A AU - Riemersma SA FAU - Jordanova, Ekaterina S AU - Jordanova ES FAU - Kok, Klaas AU - Kok K FAU - Rosenwald, Andreas AU - Rosenwald A FAU - de Jong, Daphne AU - de Jong D FAU - Schuuring, Ed AU - Schuuring E FAU - Kluin, Philip M AU - Kluin PM LA - eng PT - Journal Article PL - United States TA - Clin Cancer Res JT - Clinical cancer research : an official journal of the American Association for Cancer Research JID - 9502500 RN - 0 (HLA-D Antigens) SB - IM MH - Centromere/genetics MH - Chromosomes, Human, Pair 6 MH - Gene Expression Regulation, Neoplastic/*immunology MH - HLA-D Antigens/*genetics MH - Humans MH - In Situ Hybridization, Fluorescence MH - Lymph Nodes/immunology/pathology MH - Lymphoma, B-Cell/genetics/*immunology/pathology MH - Lymphoma, Large-Cell, Immunoblastic/genetics/immunology/pathology MH - Major Histocompatibility Complex MH - Male MH - Oligonucleotide Array Sequence Analysis MH - Sequence Deletion MH - Telomere/genetics MH - Testis/immunology EDAT- 2006/05/06 09:00 MHDA- 2006/08/22 09:00 CRDT- 2006/05/06 09:00 PHST- 2006/05/06 09:00 [pubmed] PHST- 2006/08/22 09:00 [medline] PHST- 2006/05/06 09:00 [entrez] AID - 12/9/2698 [pii] AID - 10.1158/1078-0432.CCR-05-2617 [doi] PST - ppublish SO - Clin Cancer Res. 2006 May 1;12(9):2698-705. doi: 10.1158/1078-0432.CCR-05-2617.