T Cell ExTRECT

• T Cell ExTRECT is a methodology that uses DNA sequencing data to accurately quantify T cell fraction in tumours, with results that positively correlate with other validated methods of immune measurement.
• T Cell ExTRECT measures T cell fraction directly from DNA, and therefore without the need for other data sources, which is both less expensive and saves time compared to existing methods of measuring tumour immune content.
• Data from T Cell ExTRECT have been shown both to be predictive of response to checkpoint inhibitors and associated with prognosis in lung adenocarcinoma.
• T Cell ExTRECT can be applied to both whole exome sequencing data and or whole genome sequencing data and can be incorporated into gene panels at low cost.
• 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.

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 an informatic method of DNA sequencing analysis that allows T cell fraction in tumours to be estimated. T cell diversity is a product of VDJ recombination in the TCRA gene that encodes the alpha chain of the T cell receptor.  VDJ recombination results in the excision of select gene segments from the TCRA gene as T cell receptor excision circles (TRECS), hence the name of the technology. T Cell ExTRECT measures the “read depth ratio” of the VDJ sequence in the TCRA gene using DNA sequencing data 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 in a more cost-efficient way compared to RNA sequencing methods.​ Furthermore, a low T Cell ExTRECT score was 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.