The immunogenicity of cancer mutations and implications for T cell therapy

Cancer cells can accumulate hundreds of mutations during tumor development. Some of these mutations can be recognized as “non-self” by the adaptive immune system and elicit an effective immune response (1,2). Increasing evidence suggests that T cell reactivity to these mutation-derived neoantigens has a critical role in the clinical response to immune checkpoint blockade therapies (3-8). For a mutation to be immunogenic, the protein has to be processed, and the resulting neopeptide must be able to bind to the major histocompatibility complex (MHC) in order to be presented on the cell surface. The neopeptide, once presented on the cell surface, has to be recognized by a T cell, which means that the T cell receptor (TCR) must interact strongly with the neopeptide-MHC complex (9). In a fascinating study, Tran and colleagues (10) examined how many mutations are immunogenic per tumor in nine patients with metastatic gastrointestinal cancers and whether these immunogenic neopeptides could potentially be used for the development of adoptive T cell therapies.