Proteogenomic discovery of cancer antigens: Neoantigens and beyond

Host T cells infiltrate the cancer lesion and contribute to patient survival. T cells recognize antigen peptides displayed by the cancer cell human leukocyte antigen (HLA) system. Cancer antigens constitute an essential element of T-cell discrimination and play an indispensable role in anti-cancer responses. HLA ligandome analysis directly and comprehensively detects the peptides that are naturally presented by HLA of given cells, leading to discovery of cancer antigens. A proteogenomic approach, which combines conventional proteomics with genomic information, has further deciphered the landscape of the cancer HLA ligandome. Neoantigens that arise from somatic mutations are arguably the major type of peptides patient T cells recognize. Moreover, cancer cells present peptides derived from alleged noncoding regions, which also elicit T-cell responses thereby serving as cancer antigens. The diversity of newly discovered antigen sources implies that T cells are capable of sensing a variety of genomic aberrations in cancer.