title: Immune DNA signature of T-cell infiltration in breast tumor exomes.
abstract: Tumor infiltrating lymphocytes (TILs) have been associated with favorable prognosis in multiple tumor types. The Cancer Genome Atlas (TCGA) represents the largest collection of cancer molecular data, but lacks detailed information about the immune environment. Here, we show that exome reads mapping to the complementarity-determining-region 3 (CDR3) of mature T-cell receptor beta (TCRB) can be used as an immune DNA (iDNA) signature. Specifically, we propose a method to identify CDR3 reads in a breast tumor exome and validate it using deep TCRB sequencing. In 1,078 TCGA breast cancer exomes, the fraction of CDR3 reads was associated with TILs fraction, tumor purity, adaptive immunity gene expression signatures and improved survival in Her2+ patients. Only 2/839 TCRB clonotypes were shared between patients and none associated with a specific HLA allele or somatic driver mutations. The iDNA biomarker enriches the comprehensive dataset collected through TCGA, revealing associations with other molecular features and clinical outcomes.
authors.affiliation: Division of Biomedical Informatics, Department of Medicine, University of California San Diego, United States.|Bioinformatics and Systems Biology Graduate Program, University of California San Diego, United States.
authors.forename: Eric
authors.initials: E
authors.lastname: Levy
authors.affiliation: Bioinformatics and Systems Biology Graduate Program, University of California San Diego, United States.|Division of Medical Genetics, Department of Medicine, University of California San Diego, United States.
authors.forename: Rachel
authors.initials: R
authors.lastname: Marty
authors.affiliation: Centro de Investigación y Tratamiento del Cancer, Facultad de Medicina, Universidad de Chile, Santiago, Chile.|Center for Excellence in Precision Medicine, Pfizer Chile, Santiago, Chile.
authors.forename: Valentina
authors.initials: V
authors.lastname: Gárate Calderón
authors.affiliation: Moores Cancer Center, University of California San Diego, United States.
authors.forename: Brian
authors.initials: B
authors.lastname: Woo
authors.affiliation: Division of Biomedical Informatics, Department of Medicine, University of California San Diego, United States.|Bioinformatics and Systems Biology Graduate Program, University of California San Diego, United States.
authors.forename: Michelle
authors.initials: M
authors.lastname: Dow
authors.affiliation: Centro de Investigación y Tratamiento del Cancer, Facultad de Medicina, Universidad de Chile, Santiago, Chile.|Center for Excellence in Precision Medicine, Pfizer Chile, Santiago, Chile.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Armisen
authors.affiliation: Division of Medical Genetics, Department of Medicine, University of California San Diego, United States.|Moores Cancer Center, University of California San Diego, United States.|Institute for Genomic Medicine, University of California San Diego, United States.
authors.forename: Hannah
authors.initials: H
authors.lastname: Carter
authors.affiliation: Division of Biomedical Informatics, Department of Medicine, University of California San Diego, United States.|Moores Cancer Center, University of California San Diego, United States.
authors.forename: Olivier
authors.initials: O
authors.lastname: Harismendy
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics*; D022801:Complementarity Determining Regions / Q000235:genetics; D059472:Exome / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D019674:Genes, T-Cell Receptor beta / Q000235:genetics*; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000166:cytology / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
chemical_list: D022801:Complementarity Determining Regions; D016693:Receptors, Antigen, T-Cell, alpha-beta