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

TitleImmune DNA signature of T-cell infiltration in breast tumor exomes.
Publication TypeJournal Article
Year of Publication2016
AuthorsLevy, E, Marty, R, Calderón, VGárate, Woo, B, Dow, M, Armisen, R, Carter, H, Harismendy, O
JournalSci Rep
Volume6
Pagination30064
Date Published2016
ISSN2045-2322
Abstract<p>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.</p>
DOI10.1038/srep30064
Alternate JournalSci Rep
PubMed ID27452728
PubMed Central IDPMC4958917