Targeting components of the antigen processing and presentation machinery to discover novel targets for immunotherapy.

Cells continuously present peptides on the cell surface in complex with HLA molecules. These peptides provide a snapshot into the health of the cell and a means for immunosurveillance. The antigen presentation and processing machinery (APPM) is responsible for HLA-peptide presentation, but due to gain/loss of function mutations in cancers, these components are often dysregulated, preventing peptide presentation and leading to immune evasion. In this study, we examine the role different APPM components play in peptide presentation, using a panel of patient-derived cell lines and the potent immune modulator interferon gamma (IFNγ). Our study reveals insights into how loss of specific APPM components alters the peptide repertoire. Furthermore, we find that IFNγ stimulation of cells can significantly enhance HLA-peptide presentation, while also broadening the available repertoire of clinically relevant T-cell targets.