Immunogenicity of somatic mutations in human gastrointestinal cancers

Abstract

It is unknown whether the human immune system frequently mounts a Tcell response against mutations expressed by common epithelial cancers. Using a next-generationsequencing approach combined with high-throughput immunologic screening, we demonstrated that tumor-infiltrating lymphocytes (TILs) from 9 out of 10 patients withmetastatic gastrointestinal cancers contained CD4+ and/or CD8+ Tcells that recognized one to three neo-epitopes derived from somatic mutations expressed by the patient's owntumor. There were no immunogenic epitopes shared between these patients. However, we identified in one patient a human leukocyte antigen-C∗08:02-restricted Tcell receptorfrom CD8+ TILs that targeted the KRASG12D hotspot driver mutation found in many human cancers. Thus, a high frequency of patients with common gastrointestinal cancers harborimmunogenic mutations that can potentially be exploited for the development of highly personalized immunotherapies.