150,000+ Patient Samples Speed T-Cell Receptor Discovery

Analyzing a massive collection of data from 150,000 patient tumor samples, researchers have identified T cell receptors against cancer that are shared across multiple patients. By presenting a pipeline to uncover "public" T cell receptors, their experiments could accelerate efforts to use these receptors in immunotherapies against multiple types of cancer. T cells contain T cell receptors in their cell membranes that are specific to tumor antigens. Because of this, T cell receptors offer a route to target tumor cells specifically. Thus, scientists believe the receptors could inform new anticancer therapies. However, T cell receptors are very diverse, and current techniques to discover new T cell receptors require labor-intensive workflows and difficult-to-acquire tissue specimens. Here, Emily Jackson and colleagues demonstrate that public datasets from large patient cohorts offer a more practical source for T cell receptor discovery. They constructed a database comprising bulk RNA sequencing data, clinical records, and T cell receptor chains from more than 150,000 patients with more than 30 different types of advanced cancer. The team then developed an analytical pipeline to comb through the 26 million unique T cell receptor chains. This method uncovered receptors associated with common cancer antigens, such as mutated KRAS protein and human papillomavirus proteins. Furthermore, they characterized 11 families of T cell receptors that were shared across multiple patient populations, including nine previously unknown receptor families. "More broadly, our findings demonstrate that patient-derived immune repertoires captured during routine clinical testing represent a valuable and largely untapped resource for cancer immunotherapy discovery," Jackson et al. conclude.