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Updated: Oct 21, 2025

Determination of Immune Cell Identity and Purity Using Epigenetic-Based Quantitative PCR

Determination of Immune Cell Identity and Purity Using Epigenetic-Based Quantitative PCR

Published on: February 19, 2020

Using DNA sequencing data to quantify T cell fraction and therapy response.

Robert Bentham^1,2, Kevin Litchfield^2,3, Thomas B K Watkins⁴

¹Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.

|September 9, 2021

Summary

A new method, T cell ExTRECT, estimates T cell fraction from whole-exome sequencing data. This approach aids in predicting immunotherapy response and understanding tumour immune infiltration across various cancers.

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Published on: January 7, 2019

Area of Science:

Oncology
Immunology
Genomics

Background:

The tumor microenvironment impacts cancer progression and immunotherapy effectiveness.
Accurate measurement of tumor-infiltrating lymphocytes (TILs) is crucial but often limited by data availability.
Whole-exome sequencing (WES) is commonly used for tumor mutational burden and mutation identification.

Purpose of the Study:

To develop a novel method, T cell ExTRECT, for estimating T cell fraction from WES data.
To validate the correlation of T cell ExTRECT with existing TIL measurements and assess its prognostic and predictive value.
To explore the diversity of immune infiltration in pan-cancer cohorts and identify genetic factors associated with T cell infiltration.

Main Methods:

Developed T cell ExTRECT, a method utilizing T cell receptor excision circle (TREC) loss signal from WES data.
Validated TCRA T cell fraction against orthogonal TIL estimates across different sample types.
Conducted a meta-analysis of immunotherapy-treated tumors and analyzed a pan-cancer cohort.

Main Results:

TCRA T cell fraction showed strong correlation with TIL estimates and was agnostic to sample type.
Blood TCRA T cell fraction was higher in females and correlated with tumor immune infiltrate and bacterial reads.
Tumor TCRA T cell fraction predicted prognosis in lung adenocarcinoma and immunotherapy response in a meta-analysis.
Subclonal loss at 12q24.31-32 was associated with reduced TCRA T cell fraction.

Conclusions:

T cell ExTRECT offers a cost-effective method to assess immune infiltration from WES data.
This method provides valuable prognostic and predictive information for cancer patients, especially those undergoing immunotherapy.
T cell ExTRECT enhances our understanding of tumor immune heterogeneity and its genetic underpinnings.