Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2017 Nov 28;114(48):E10409-E10417. doi: 10.1073/pnas.1713863114. Epub 2017 Nov 14.

T cell receptor sequencing of early-stage breast cancer tumors identifies altered clonal structure of the T cell repertoire.

Author information

1
Department of Bioengineering, Stanford University, Stanford, CA 94305.
2
Department of Surgery, Stanford University School of Medicine, Stanford, CA 94305.
3
Department of Bioengineering, Stanford University, Stanford, CA 94305; quake@stanford.edu.
4
Department of Applied Physics, Stanford University, Stanford, CA 94305.
5
Chan Zuckerberg Biohub, San Francisco, CA 94518.

Abstract

Tumor-infiltrating T cells play an important role in many cancers, and can improve prognosis and yield therapeutic targets. We characterized T cells infiltrating both breast cancer tumors and the surrounding normal breast tissue to identify T cells specific to each, as well as their abundance in peripheral blood. Using immune profiling of the T cell beta-chain repertoire in 16 patients with early-stage breast cancer, we show that the clonal structure of the tumor is significantly different from adjacent breast tissue, with the tumor containing ∼2.5-fold greater density of T cells and higher clonality compared with normal breast. The clonal structure of T cells in blood and normal breast is more similar than between blood and tumor, and could be used to distinguish tumor from normal breast tissue in 14 of 16 patients. Many T cell sequences overlap between tissue and blood from the same patient, including ∼50% of T cells between tumor and normal breast. Both tumor and normal breast contain high-abundance "enriched" sequences that are absent or of low abundance in the other tissue. Many of these T cells are either not detected or detected with very low frequency in the blood, suggesting the existence of separate compartments of T cells in both tumor and normal breast. Enriched T cell sequences are typically unique to each patient, but a subset is shared between many different patients. We show that many of these are commonly generated sequences, and thus unlikely to play an important role in the tumor microenvironment.

KEYWORDS:

T cell receptor; breast cancer; repertoire sequencing

PMID:
29138313
PMCID:
PMC5715779
DOI:
10.1073/pnas.1713863114
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center