Immunogenicity of somatic mutations in human gastrointestinal cancers
Top Cited Papers
- 11 December 2015
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 350 (6266), 1387-1390
- https://doi.org/10.1126/science.aad1253
Abstract
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 (TILs) from 9 out of 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, we identified in one patient a human leukocyte antigen–C*08:02–restricted T cell receptor from CD8+ TILs 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 that can potentially be exploited for the development of highly personalized immunotherapies.Keywords
Funding Information
- National Cancer Institute
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