Immune DNA signature of T-cell infiltration in breast tumor exomes

Sci Rep. 2016 Jul 25:6:30064. doi: 10.1038/srep30064.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptive Immunity / genetics
  • Breast Neoplasms / genetics*
  • Complementarity Determining Regions / genetics
  • Exome / genetics*
  • Female
  • Gene Expression Profiling
  • Genes, T-Cell Receptor beta / genetics*
  • Humans
  • Lymphocytes, Tumor-Infiltrating / cytology
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Receptors, Antigen, T-Cell, alpha-beta / genetics*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*

Substances

  • Complementarity Determining Regions
  • Receptors, Antigen, T-Cell, alpha-beta