The more T cells a patient has, the more likely they are to benefit from immunotherapies like checkpoint inhibitor therapy. Therefore, estimating the number of T cells in a tumor sample can help a clinician determine the best cancer-fighting strategy for the patient. 

Many techniques for accurately tracking T cells are inconvenient or are not commonly used by researchers or clinics, but DNA sequencing is a common technique in many labs. Now, researchers have found a way to use DNA sequencing to estimate the number of T cells in a sample.

Described in Nature, the tools T cell receptor excision circle (TREC) and T cell ExTRECT work by parsing a reduction in sequencing depth. By scoring specific sequencing signals, the tool allows researchers to estimate the fraction of T cells in a tumor sample by scanning the whole exome sequencing data.

A lot of researchers sequence DNA, said Robert Bentham, a computational biologist at the University College London Cancer Institute who led the study. “[T cell ExTRECT is] really useful in a lot of cases where you might have only DNA data, and we were just trying to demonstrate, if you want to ask questions about the immune system, you can use this metric.”

Bentham added that many researchers have exome sequencing data left over from previous studies that can be re-analyzed with T cell ExTRECT, which is one of the tool’s biggest strengths. “You can revisit those studies that you have the data for, quickly run this tool, and effectively generate new data. Maybe you’ll be able to look at the immune system in these old data sets, and that could tell you something novel that you hadn’t previously noticed.”

The authors also performed a meta-analysis on tumors treated with immunotherapy and found that T cell ExTRECT predicted the tumor’s response to immunotherapy. The novelty of the finding is not that the presence of T cells predicts the immunotherapy response, but that DNA sequencing could be used to make the prediction.

While T cell ExTRECT has only been tested in the lab and has not yet been proven for the clinic, Eytan Ruppin, a computational biologist from the National Cancer Institute who was not involved in the study, remarked that the tool has broad implications. “The work is — to use a bombastic word — pioneering, potentially groundbreaking because it’s not only a wonderful result, but it’s opened up so many potential real additional research questions and opportunities to explore.”

Reference

Bentham, R. et al. Using DNA sequencing data to quantify T cell fraction and therapy response. Nature  597, 555-560 (2021).