Endoplasmic reticulum
aminopeptidase 1 and 2 (ERAP1 and ERAP2) are key components on the pathway that generates antigenic
epitopes for presentation to cytotoxic T-lymphocytes (CTLs). Coding single nucleotide polymorphisms (SNPs) in these
enzymes have been associated with pre-disposition to several major human diseases including inflammatory diseases with autoimmune etiology,
viral infections, and virally induced
cancer. The function of these
enzymes has been demonstrated to affect CTL and natural killer cell responses toward healthy and malignant cells as well as the production of inflammatory
cytokines. Recent studies have demonstrated that SNPs in ERAP1 and ERAP2 can affect their ability to generate or destroy antigenic
epitopes and define the immunopeptidome. In this review, we examine the potential role of these
enzymes and their polymorphic states on the generation of cytotoxic responses toward malignantly transformed cells. Given the current state-of-the-art, it is possible that polymorphic variation in these
enzymes may contribute to the individual's pre-disposition to
cancer through altered generation or destruction of
tumor antigens that can facilitate tumor immune evasion.