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Science. 2015 Dec 11;350(6266):1387-90. doi: 10.1126/science.aad1253. Epub 2015 Oct 29.

Immunogenicity of somatic mutations in human gastrointestinal cancers.

Author information

1
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
2
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. sar@mail.nih.gov.

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 KRAS(G12D) 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.

PMID:
26516200
DOI:
10.1126/science.aad1253
[Indexed for MEDLINE]
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