Endoplasmic Reticulum Aminopeptidase 2, a common immunological link to adverse pregnancy outcomes and cancer clearance?

Endoplasmic Reticulum Aminopeptidase 2 (ERAP2) trims HLA class I-binding peptides, determining the peptide repertoire presented for immune recognition. Variation in the ERAP2 amino acid sequence could affect the ability of some fetuses and tumors to achieve immune evasion. For example, homozygosity for an ERAP2 variant that has increased trimming efficiency for hydrophobic molecules has never been detected in mothers and fetuses. Thus, it is possible that this single nucleotide polymorphism (SNP) in the ERAP2 gene has been selected against in order to prevent alteration of the immune privileged uterine environment, and to allow tumors to escape immune recognition. Currently, there are no immunological treatments or prophylactic approaches to ensure a healthy pregnancy outcome, and the success of cancer immunotherapies is variable. Understanding the role of ERAP2 in immune evasion mechanisms in pregnancy and cancer may improve fetal survival and tumor clearance. This review summarizes current knowledge about ERAP2 and its N392 variant, and their relationship to pregnancy outcomes and cancer immune evasion/recognition.