The major histocompatibility complex (MHC) is located on chromosome 6 and contains more than 200 genes. There are separate clusters of MHC class I genes, MHC class II genes, and MHC class III genes. These genes are also known as Human Leukocyte Antigen (HLA) genes. HLA-E is an MHC molecule belonging to the non-classical MHC class I (Ib) and is involved in both innate and adaptive immunity. As such, HLA-E has been identified as a ligand for the CD94/NKG2 receptors expressed on NK cells and a subset of T-cells, but also for the T-cell receptor on NK cytotoxic T-cells. Consequently, when HLA-E is expressed on cancer cells, it directly suppresses innate and adaptive immunity. HLA-E enrichment has been associated with various types of cancer and is often linked to worse prognosis.