The elimination of tumors through vaccination or the adoptive transfer of tumor-specific T cells is an attractive option but is technically challenging because of difficulties in raising robust and appropriate immune responses. In Science, Schumacher and colleagues study patients with melanoma and find that their endogenous anti-tumor responses are poor, most probably due to immunoediting. Therefore, the authors turn to healthy donors as a potential source of reactivity of the T cell antigen receptor to melanoma neoantigens. An HLA-binding screen of potential melanoma neopeptides reveals a much greater number of healthy donor T cells that recognize melanoma. Many of these donor-derived T cell antigen receptors can be successfully introduced into recipient T cells, which can result in specific recognition of tumor neoantigens. These findings reveal that donors can act as a rich source of neoantigen reactivity, and this could inform their use in adoptive cancer immunotherapy.

Science 352, 1337–1341 (2016)