Immunotherapies can mediate regression of human tumors with high mutation rates, but responses are rarely observed in patients with common epithelial can-cers. This raises the question of whether patients with these common cancers harbor T lymphocytes that recognize mutant proteins expressed by autologous tumors that may represent ideal targets for immunotherapy. Using high-throughput immunologic screening of mutant gene products identified via whole-exome sequencing, we identified neoantigen-reactive tumor-infiltrating lymphocytes (TIL) from 62 of 75 (83%) patients with common gastrointestinal cancers. In total, 124 neoantigen-reactive TIL populations were identified, and all but one of the neoantigenic determinants were unique. The results of in vitro T-cell recognition assays demonstrated that 1.6% of the gene products encoded by somatic nonsynonymous mutations were immunogenic. These findings demonstrate that the majority of common epithelial cancers elicit immune recognition and open possibilities for cell-based immunotherapies for patients bearing these cancers. SIGNIFICANCE: TILs cultured from 62 of 75 (83%) patients with gastrointestinal cancers recognized neoantigens encoded by 1.6% of somatic mutations expressed by autologous tumor cells, and 99% of the neoantigenic determinants appeared to be unique and not shared between patients.
Parkhurst, M. R., Robbins, P. F., Tran, E., Prickett, T. D., Gartner, J. J., Li, J., … Rosenberg, S. A. (2019). Unique neoantigens arise from somatic mutations in patients with gastrointestinal cancers. Cancer Discovery, 9(8), 1022–1035. https://doi.org/10.1158/2159-8290.CD-18-1494