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Immunogenicity of somatic mutations in human gastrointestinal cancers

2015; American Association for the Advancement of Science; Volume: 350; Issue: 6266 Linguagem: Inglês

10.1126/science.aad1253

1095-9203

Eric Tran, Mojgan Ahmadzadeh, Yong‐Chen Lu, Alena Gros, Simon Turcotte, Paul F. Robbins, Jared J. Gartner, Zhili Zheng, Yong F. Li, Satyajit Ray, John R. Wunderlich, Robert Somerville, Steven A. Rosenberg,

Genetic factors in colorectal cancer

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.