Imperial College London
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Professor Anand Devaraj

Faculty of Medicine, National Heart & Lung Institute

Professor of Practice (Thoracic Radiology)
 
 
 
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Contact

 

anand.devaraj Website

 
 
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Location

 

South BlockRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@article{Bentham:2021:10.1038/s41586-021-03894-5,
author = {Bentham, R and Litchfield, K and Watkins, TBK and Lim, EL and Rosenthal, R and Martínez-Ruiz, C and Hiley, CT and Bakir, MA and Salgado, R and Moore, DA and Jamal-Hanjani, M and TRACERx, Consortium and Swanton, C and McGranahan, N},
doi = {10.1038/s41586-021-03894-5},
journal = {Nature},
pages = {555--560},
title = {Using DNA sequencing data to quantify T cell fraction and therapy response.},
url = {http://dx.doi.org/10.1038/s41586-021-03894-5},
volume = {597},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The immune microenvironment influences tumour evolution and can be both prognostic and predict response to immunotherapy1,2. However, measurements of tumour infiltrating lymphocytes (TILs) are limited by a shortage of appropriate data. Whole-exome sequencing (WES) of DNA is frequently performed to calculate tumour mutational burden and identify actionable mutations. Here we develop T cell exome TREC tool (T cell ExTRECT), a method for estimation of T cell fraction from WES samples using a signal from T cell receptor excision circle (TREC) loss during V(D)J recombination of the T cell receptor-α gene (TCRA (also known as TRA)). TCRA T cell fraction correlates with orthogonal TIL estimates and is agnostic to sample type. Blood TCRA T cell fraction is higher in females than in males and correlates with both tumour immune infiltrate and presence of bacterial sequencing reads. Tumour TCRA T cell fraction is prognostic in lung adenocarcinoma. Using a meta-analysis of tumours treated with immunotherapy, we show that tumour TCRA T cell fraction predicts immunotherapy response, providing value beyond measuring tumour mutational burden. Applying T cell ExTRECT to a multi-sample pan-cancer cohort reveals a high diversity of the degree of immune infiltration within tumours. Subclonal loss of 12q24.31-32, encompassing SPPL3, is associated with reduced TCRA T cell fraction. T cell ExTRECT provides a cost-effective technique to characterize immune infiltrate alongside somatic changes.
AU  - Bentham,R
AU  - Litchfield,K
AU  - Watkins,TBK
AU  - Lim,EL
AU  - Rosenthal,R
AU  - Martínez-Ruiz,C
AU  - Hiley,CT
AU  - Bakir,MA
AU  - Salgado,R
AU  - Moore,DA
AU  - Jamal-Hanjani,M
AU  - TRACERx,Consortium
AU  - Swanton,C
AU  - McGranahan,N
DO  - 10.1038/s41586-021-03894-5
EP  - 560
PY  - 2021///
SP  - 555
TI  - Using DNA sequencing data to quantify T cell fraction and therapy response.
T2  - Nature
UR  - http://dx.doi.org/10.1038/s41586-021-03894-5
UR  - https://www.ncbi.nlm.nih.gov/pubmed/34497419
VL  - 597
ER  -
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