The
Human Leukocyte Antigen class I (HLA-I) system is an essential part of the immune system that is fundamental to the successful activation of cytotoxic lymphocytes, and an effective subsequent immune attack against both pathogen-infected and
cancer cells. The importance of cytotoxic T cell activity and ability to detect foreign
cancer-related antigenic
peptides has recently been highlighted by the successful application of
monoclonal antibody-based checkpoint inhibitors as novel immune
therapies. Thus, there is an increased interest in fully characterising the repertoire of
peptides that are being presented to cytotoxic CD8+ T cells by
cancer cells. However, HLA-I is also known to be present on the surface of extracellular vesicles, which are released by most if not all
cancer cells. Whilst the
peptide ligandome presented by cell surface HLA class I molecules on
cancer cells has been studied extensively, the ligandome of extracellular vesicles remains relatively poorly defined. Here, we will describe the current understanding of the HLA-I
peptide ligandome and its role on
cancer-derived extracellular vesicles, and evaluate the aspects of the system that have the potential to advance immune-based therapeutic approaches for the effective treatment of
cancer.