Researchers from the Garvan Institute of Medical Research have developed a new method to spot rare immune cells that are reactive against cancer cells—from within a patient’s own immune system. According to the researchers, the ability to find and barcode these rare cells has the power to guide individualized treatment strategies. The results were published today in Nature Communications.
The method, dubbed ‘RAGE-seq,’ enables scientists to track how immune cells evolve inside tumor tissue, providing insight into how to better arm the immune system to target cancer. The technique can be likened to a barcode tracker, as it is able to scan detailed information from thousands of immune cells at a time.
“The immune cells that recognize cancer cells are often rare,” says senior author Alex Swarbrick. “We have to sort through thousands of cells to find these replicating cells that may make up only a small fraction of all the immune cells present in a tumor.”
Previous methods have made it possible to read the RNA that encodes an immune cell’s receptor from single cells. But they have not had the capacity to sort through the thousands of cells present in a tumor all at once. Thus, the researchers developed a new method by harmonizing different genomic technologies.
First, they developed a way to enrich the RNA from single cells, targeting the RNAs encoding the immune cell receptors. Next, they developed a computational tool to accurately read full-length sequences of the immune cell receptors. The resulting method was named Repertoire and Gene Expression by Sequencing (RAGE-seq), and it works much like a barcode tracker. By ‘scanning’ the relevant immune cell receptors in many thousands of cells at once, it can provide an accurate snapshot of how the immune cells in a tissue sample are related—and which cells may be effective at mounting a response against cancer.
The researchers then carried out a proof-of-principle study in a breast cancer patient. They used the new method to sample 7,138 cells from the tumor and associated lymph node, and they pinpointed a number of related cells that were present in both tissues. This revealed specific genetic signatures of the immune response within the patient’s tumor.
The team is now applying the technique to samples from melanoma patients to understand why half of patients receiving immunotherapy have a poor response. The researchers believe that the method could also be used to study autoimmune and inflammatory diseases.
Image: Garvan scientists have developed a way to spot rare immune cells, by revealing RNA 'barcodes' of immune cell receptors. Image courtesy of Dr. Martin Smith.