Immunogenicity of somatic mutations in human gastrointestinal cancers

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Science  29 Oct 2015:
DOI: 10.1126/science.aad1253

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It is unknown whether the human immune system frequently mounts a T-cell response against mutations expressed by common epithelial cancers. Using a next-generation sequencing approach combined with high-throughput immunologic screening, we demonstrated that tumor-infiltrating lymphocytes (TIL) from 9/10 patients with metastatic gastrointestinal cancers contained CD4+ and/or CD8+ T cells that recognized one to three neo-epitopes derived from somatic mutations expressed by the patient's own tumor. There were no immunogenic epitopes shared between these patients. However, in one patient we identified a human leukocyte antigen (HLA)-C*08:02-restricted T-cell receptor from CD8+ TIL that targeted the KRASG12D hotspot driver mutation found in many human cancers. Thus, a high frequency of patients with common gastrointestinal cancers harbor immunogenic mutations which could potentially be exploited for the development of highly personalized immunotherapies.

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