Immunogenicity of somatic mutations in human gastrointestinal cancers

E Tran, M Ahmadzadeh, YC Lu, A Gros, S Turcotte… - Science, 2015 - science.org
E Tran, M Ahmadzadeh, YC Lu, A Gros, S Turcotte, PF Robbins, JJ Gartner, Z Zheng, YF Li…
Science, 2015science.org
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 …
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.
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