[Proteogenomics HLA Ligandome Analysis for Cancer Antigen Research]

Immune checkpoint blockades have brought about great benefits to cancer patient survival; however, the effect is yet limited and the overall objective rates are not satisfactory across cancer types. Understanding T cell discrimination against cancer and development of biomarkers are both indispensable for future application. In this brief review, we introduce proteogenomics HLA ligandome analysis, which combines conventional proteomics using mass spectrometry with genomic analysis data. The approach directly and comprehensively captures immunopeptidome of cancer cells, revealing an unprecedented number of antigens that can be targeted by T cells. Intriguingly, the repertoire comprises unique classes of peptides: neoantigens that arise from gene mutation, spliced peptides generated by the proteasomes, and non-coding region derived peptides. These findings demonstrate the diversity of T cell discrimination against cancer cells, and the accumulation of individual antigen data would contribute to development of precision medicine.