The recent success of
monoclonal antibody checkpoint inhibitor
therapies that enhance the ability of CD8+ T cells to detect
cancer-related antigenic
peptides has refocused the need to fully understand the repertoire of
peptides being presented to the immune system. Whilst the
peptide ligandome presented by cell surface human leucocyte
antigen class I (HLA-I) molecules on
cancer cells has been studied extensively, the ligandome of extracellular vesicles (EVs) remains poorly defined. Here, we report the HLA-I ligandome of both the cell surface and EVs from eight
breast cancer cell lines (MCF7, MDA-MB-231, MDA-MB-361, MDA-MB-415, MDA-MB-453, HCC 1806, HCC 1395, and HCC 1954), and additionally the
melanoma cell line ESTDAB-056 and the
multiple myeloma line RPMI 8226. Utilizing HLA-I immunoisolation and mass spectrometry, we detected a total of 6574
peptides from the cell surface and 2461
peptides from the EVs of the cell lines studied. Within the EV HLA-I ligandome, we identified 150
peptides derived from tumour associated antigenic
proteins, of which 19
peptides have been shown to elicit T-cell responses in previous studies. Our data thus show the prevalence of clinically relevant tumour-associated antigenic
peptides in the HLA-I ligandome presented on EV.