New Tool Uses Sequencing Data for T Cell Quantification

Scientists at UCL and the Francis Crick Institute have developed a new tool that they say can rapidly estimate the number of T cells in a cancerous tumor. As T cell abundance can help predict a patient’s response to immunotherapy, the team is hopeful this development could enable more targeted and effective cancer therapies.

As part of the project, the team analyzed DNA sequencing data from tumors to see if they could quantify the fraction of T cells within a sample. According to Nicholas McGranahan, corresponding author of the paper published in Nature today, “DNA sequencing is frequently performed on cancer patient’s tumors for patient stratification and to understand how a cancer has developed. Estimation of immune cells, which are important for controlling cancers, influencing patient survival and guiding treatment, has in the past not been possible to estimate solely from DNA sequencing data. We aimed to explore whether we could develop a novel method to elucidate immune cells directly from DNA sequencing, without the need for more data.”

In this research, the team developed a tool a way to “look back” and calculate levels of T cell VDJ recombination, which is a process in T cells in which they are reassembled or altered and given the tools to identify and attack invaders.

Specifically, the team found a signal that indicated the loss of T cell receptor excision circles (TRECs) needed for T cell maturation, which occurred during VDJ recombination. By giving this “loss” a score, they were able to estimate accurately the number of T cells present in the tumor.

The score can also be applied to DNA sequencing data derived from normal blood samples that are typically collected but have not been able to be systematically analyzed for immune content.