RT Journal Article
SR Electronic
T1 Immune DNA signature of T-cell infiltration in breast tumor exomes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 047753
DO 10.1101/047753
A1 Eric Levy
A1 Rachel Marty
A1 Valentina Garate-Calderon
A1 Brian Woo
A1 Michelle Dow
A1 Ricardo Armisen
A1 Hannah Carter
A1 Olivier Harismendy
YR 2016
UL http://biorxiv.org/content/early/2016/04/08/047753.abstract
AB 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.