Tumour and placenta establishment: The importance of antigen processing and presentation

Abstract

Classical and non-classical MHC class I (MHC I) molecules displayed at the cell surface are essential for the induction of innate and adaptive immune responses. Classical MHC I present endogenously derived peptides to CD8+ T cells for immunosurveillance of infected or malignant cells. By contrast, non-classical MHC I, in particular HLA-G, also display peptides, but primarily act as immunomodulatory ligands for the innate immune response and are an important component for extravillous trophoblast invasion to form the placenta in pregnancy. Endoplasmic Reticulum AminoPeptidase 1 (ERAP1), which trims peptides in the ER to generate ligands for MHC I loading, is a key regulator of the peptide repertoire and has a significant impact on the formation of stable MHC I at the cell surface. ERAP1 also plays a role in angiogenesis, cell cycle progression and migration, events that are shared between tumour cells and placenta formation. Here we discuss the similarities between tumour and extravillous trophoblast cells in their immune modulatory, invasion, migration and proliferation properties in the context of ERAP1 and its role in establishment of solid tumours and placenta formation.