β2-microglobulin gene mutation is not a common mechanism of HLA class I total loss in human tumors

Major histocompatibility (MHC) class I molecules play an important role in cell recognition against virus-infected and tumor cells. Their main function is to present peptides derived from intracellular proteins to cytotoxic T-lymphocytes (CTL). The correct assembly of MHC class I peptide complexes is required for the stable expression of HLA class I [l]. This assembly occurs in the endoplasmic reticulum, where endogenous β2-microglobulin (β2m) gene expression is necessary for proper intracellular MHC assembly and stabilization by endogenous peptides. Tumor cells frequently lose HLA molecules during tumor development [2]. These alterations in HLA gene expression can provide the tumor cells with a similar mechanism of escape from the immune system [3] to that used by some viruses [4]. Tumor cells often exhibit a complete loss of expression of HLA antigens; this is a relatively frequent phenotype (9%–52%), associated with mutations in the β2m gene or defects in the transporterassociated processing. The negative impact of β2m gene mutations on T-cell based immunotherapy has been reported [5, 6], indicating the importance of analyzing the HLA phenotype of the tumor. The aim of this study was to investigate the frequency of β2m mutations in a series of melanomas and fresh head and neck, bladder, and colorectal cancers previously studied for HLA class I antigen expression. Our results indicate that somatic β2m gene mutation in human tumors showing total loss of HLA expression is not a frequent event.