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

## TL;DR

This study introduces a new DNA-based method to measure T-cell infiltration in breast tumors using exome data, linking it to better patient outcomes.

## Contribution

A novel immune DNA signature based on TCRB CDR3 reads is proposed and validated for assessing T-cell infiltration in breast tumors.

## Key findings

- CDR3 reads from TCGA exomes correlate with TILs, tumor purity, and adaptive immunity gene expression.
- The iDNA signature is associated with improved survival in Her2+ breast cancer patients.
- Most TCRB clonotypes are unique to individual patients and not linked to HLA alleles or driver mutations.

## 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.