The cancer antigenome

Cancer cells deviate from normal body cells in two immunologically important ways. First, tumour cells carry tens to hundreds of protein‐changing mutations that are either responsible for cellular transformation or that have accumulated as mere passengers. Second, as a consequence of genetic and epigenetic alterations, tumour cells express a series of proteins that are normally not present or present at lower levels. These changes lead to the presentation of an altered repertoire of MHC class I‐associated peptides. Importantly, while there is now strong clinical evidence that cytotoxic T‐cell activity against such tumour‐associated antigens can lead to cancer regression, at present we fail to understand which tumour‐associated antigens form the prime targets in effective immunotherapies. Here, we describe how recent developments in cancer genomics will make it feasible to establish the repertoire of tumour‐associated epitopes on a patient‐specific basis. The elucidation of this ‘cancer antigenome’ will be valuable to reveal how clinically successful immunotherapies mediate their effect. Furthermore, the description of the cancer antigenome should form the basis of novel forms of personalized cancer immunotherapy.