Highlights
- T Cell ExTRECT measures T cell fraction in tumours directly from DNA sequencing data
- Less expensive and saves time compared to existing methods of measuring tumour immune content
- Shown both to be predictive of response to checkpoint inhibitors and associated with prognosis in lung adenocarcinoma
The Opportunity
The immune microenvironment influences tumour evolution and can be both prognostic and predict response to immunotherapy. In particular, the success of checkpoint inhibitor therapy (CPI) has been linked to whether there are ‘switched off’ T cells present in the tumour that CPI therapy can effectively ‘switch on’. However, measures of such tumour infiltrating lymphocytes (TILs) are limited by the shortage of appropriate data and current methods, based on RNA sequencing and histopathology, are time-consuming and expensive, resulting in their under-utilisation in clinical settings. T Cell ExTRECT offers a solution to this.
T Cell ExTRECT is a methodology that uses DNA sequencing data to accurately quantify T cell fraction in tumours. This is accomplished by measuring the “read depth ratio” of the VDJ sequence in the TCRA gene to directly estimate T cell fraction in the sample.
The accuracy of the methodology was validated using 5 orthogonal approaches, demonstrating that T Cell ExTRECT is an accurate method to estimate immune infiltrate.
By measuring T cell fraction directly from DNA, and therefore without the need for other data sources, T Cell ExTRECT saves both time and expense compared to existing methods of measuring tumour immune content, such as RNA sequencing methods. The methodology can be applied to whole exome sequencing data or whole genome sequencing data and can be incorporated into gene panels at low cost.
A low T Cell ExTRECT score was also found to be indicative of a worse prognosis in a cohort of lung adenocarcinoma patients. The clinical utility of T Cell ExTRECT was further validated when shown to be predictive of CPI therapy response across 8 main cancer types.
T Cell ExTRECT was developed by Robert Bentham, Charlie Swanton, Nicholas McGranaham and Thomas Watkins at UCL and the Francis Crick Institute.
PCT filed in July 2022 with claims covering the T Cell ExTRECT methodology.