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.
The patented 'RAGE-seq' method enables scientists to track how immune cells evolve inside tumour tissue for the first time, revealing unprecedented insight into how to better arm the immune system to target cancer. The technique can be likened 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 Professor Chris Goodnow, Executive Director of the Garvan Institute and co-senior author of the published work. "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."
Development of the method, by Dr Mandeep Singh (Immunogenomics Laboratory) and Ghamdan Al-Eryani (Tumour Progression Laboratory) at Garvan, is published in the journal Nature Communications.
Our immune system helps protect us against foreign pathogens, such as bacteria or viruses. But it often responds poorly to cancers, which arise from the body's own cells -- usually too few immune cells 'recognise' them to mount an effective immune response.
Immune cells come in many different forms -- they mix-and-match different types of 'receptors' on their cell surface, which monitor the cell's environment. When an immune cell's receptors recognise a potential hazard, the cell replicates to make more copies of itself, able to target the threat more effectively.
"The immune cells that recognise cancer cells are often rare," says Associate Professor Alex Swarbrick, who heads the Tumour Progression Laboratory at Garvan. "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 tumour."
Previous methods have made it possible to read the long stretches of genetic output (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 tumour, at a single time.
The study authors developed a new method by harmonising four different genomic technologies (Oxford Nanopore Technologies, 10X Genomics, Illumina and CaptureSeq).
[...] 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 the method could also be applied to provide a better understanding of autoimmune and inflammatory diseases.
Mandeep Singh, Ghamdan Al-Eryani, Shaun Carswell, James M. Ferguson, James Blackburn, Kirston Barton, Daniel Roden, Fabio Luciani, Tri Giang Phan, Simon Junankar, Katherine Jackson, Christopher C. Goodnow, Martin A. Smith, Alexander Swarbrick. High-throughput targeted long-read single cell sequencing reveals the clonal and transcriptional landscape of lymphocytes. Nature Communications, 2019; 10 (1) DOI: 10.1038/s41467-019-11049-4
