Gene expression analysis of immune privileged site-associated DLBCL: The effect of HLA class II downregulation

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/DR and larger hemizygous deletions of the major histocompatibility complex (MHC) region. To better understand the significance of downregulation 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 diffuse large B-cell lymphomas (DLBCL) after characterization of these deletions. Low levels of HLA-DR mRNA in whole testicular DLBCL samples were associated with a strong downregulation of numerous immune-related genes specific for T-cells, macrophages, antigen presentation and processing, lymphocyte activation, chemokines and chemokine receptors and the complement system. Interestingly, hemizygous and homozygous deletions in the MHC region did not have any additional impact on global gene expression. Keywords: Gene expression Twenty-six primary testicular DLBCL and 10 primary nodal DLBCL were analyzed using an 18k cDNA microarray. Gene expression profiles were compared between several subsets: - testicular vs nodal DLBCL - testicular DLBCL with and without deletions - testicular DLBCL with normal/high and low HLA-DR mRNA expression levels