Project description:Increased infiltration of CD3+ and CD8+ T cells into ovarian cancer (OC) tumors is linked to better prognosis, but the specific antigens involved are unclear. Recent data suggests that HLA-I can present peptides from noncoding genomic regions, known as noncanonical or cryptic peptides, but their immunogenicity is underexplored. To address this, we used immunopeptidomic analysis and RNA sequencing on five metastatic OC tumors, identifying around 311 cryptic peptides total, with 40 to 83 per patient. Over 90% of these were novel, with only 9 matching existing datasets. Despite comprising less than 1% of total peptides, noncoding cryptic peptides were more abundant than other antigen types in OC samples. Notably, about 70% of the prioritized cryptic peptides elicited T cell activation, indicated by increased 4-1BB and IFNγ expression in autologous CD8+ T cells. This study reveals noncoding cryptic peptides as a significant class of immunogenic antigens in OC.
