Tracking immune cells with a ‘barcode’

Australian researchers have developed a technique for spotting rare immune cells that are reactive against cancer cells from within a patient’s own immune system.

They liken it to a barcode tracker, able to scan detailed information from thousands of immune cells at a time.

“This method gives us the most detailed view yet of how immune cells behave in the human body,” says senior author Chris Goodnow, from the Garvan Institute of Medical Research.  

“Immune cells play a critical role in the development of disease. This method shows significant potential to help us personalise cancer treatments to the individual.” 

The new technique – known as RAGE-seq – is described in a paper in the journal Nature Communications. It was developed by Mandeep Singh from Garvan’s Immunogenomics Laboratory and Ghamdan Al-Eryani from the Tumour Progression Laboratory.

Previous approaches have been able to read the long stretches of genetic output (the RNA) that encodes an immune cell’s receptor from single cells, but have not, the researchers say, succeeded in sorting through the thousands of cells present in a tumour at a single time.

Their approach – Repertoire and Gene Expression by Sequencing, to give it its full name – was developed by harmonising four different genomic technologies. 

They first developed a way to enrich the RNA from single cells, targeting the RNAs encoding the immune cell receptors, then developed a computational tool to accurately read full-length sequences of the immune cell receptors.

By “scanning” the relevant immune cell receptors in many thousands of cells at once, RAGE-seq 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.

In a proof-of-principle study, the researchers used the method to sample 7138 cells from the tumour and associated lymph node of a breast cancer patient. 

They pinpointed a number of related cells that were present in both tissues, and which revealed specific genetic signatures of the immune response within the patient’s tumour.

They are now applying the technique to samples from melanoma patients, to understand why half of patients receiving immunotherapy have a poor response. They believe the same approach could also be applied to autoimmune and inflammatory diseases.