title: Immunogenicity of somatic mutations in human gastrointestinal cancers.
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.
authors.affiliation: Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Tran
authors.affiliation: Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Mojgan
authors.initials: M
authors.lastname: Ahmadzadeh
authors.affiliation: Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Yong-Chen
authors.initials: YC
authors.lastname: Lu
authors.affiliation: Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Alena
authors.initials: A
authors.lastname: Gros
authors.affiliation: Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Simon
authors.initials: S
authors.lastname: Turcotte
authors.affiliation: Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Paul F
authors.initials: PF
authors.lastname: Robbins
authors.affiliation: Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Jared J
authors.initials: JJ
authors.lastname: Gartner
authors.affiliation: Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Zhili
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Yong F
authors.initials: YF
authors.lastname: Li
authors.affiliation: Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Satyajit
authors.initials: S
authors.lastname: Ray
authors.affiliation: Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Wunderlich
authors.affiliation: Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Somerville
authors.affiliation: Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. sar@mail.nih.gov.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Rosenberg
mesh_terms: D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000628:therapy; D015236:HLA-C Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D016056:Immunodominant Epitopes / Q000235:genetics / Q000276:immunology; D007167:Immunotherapy / Q000379:methods; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D057285:Precision Medicine / Q000379:methods; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology; D016283:Proto-Oncogene Proteins p21(ras); D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D018631:ras Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D015236:HLA-C Antigens; C524551:HLA-C*08 antigen; D016056:Immunodominant Epitopes; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins