Researchers 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 tumor 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 the 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."
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 recognize cancer cells are often rare," says another author. "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 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 tumor, 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).
They first developed a way to enrich the RNA from single cells, targeting the RNAs encoding the immune cell receptors. They then developed a computational tool to accurately read full-length sequences of the immune cell receptors.
The resulting Repertoire and Gene Expression by Sequencing, or 'RAGE-seq', method 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.
In a proof-of-principle study, the researchers used the method to sample 7,138 cells from the tumor and associated lymph node of a breast cancer patient. The team 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 tumor.
The researchers say the ability to find and barcode these rare cells of the immune system has the power to guide treatment strategies based on the individual.
Immunotherapy is an emerging form of cancer therapy designed to activate the immune system to better target cancer, but not all patients respond well and current methods used to assess a patient's response give a poor snapshot of the behavior of their immune cells.
Professor Goodnow says there is significant interest from pharmaceutical companies to better understand the immune system's response to cancer, at a resolution now available through the RAGE-seq method. "We hope RAGE-seq will be implemented in clinical trials, providing crucial information that will help potential cancer therapeutics get to the right patients more quickly."
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.
https://www.nature.com/articles/s41467-019-11049-4
http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fhigh-throughput_3&filter=22
High through-put RAGE-seq to track the tumor lymphocytes
- 1,055 views
- Added
Edited
Latest News
Mutations in noncoding DNA…
By newseditor
Posted 24 Apr
More influence of environme…
By newseditor
Posted 24 Apr
The assembly of the human c…
By newseditor
Posted 24 Apr
Wiring of the human neocortex
By newseditor
Posted 24 Apr
Abusive drugs hijack natura…
By newseditor
Posted 23 Apr
Other Top Stories
Cell fate and transcription factors!
Read more
Cell like structures from cytoplasm!
Read more
Transcriptional dysregulation by a nucleus-localized aminoacyl-tRNA…
Read more
Autophagy supplies lipid to TSC mutated brain tumors!
Read more
Regulator of apoptotic cell death identified!
Read more
Protocols
A programmable targeted pro…
By newseditor
Posted 23 Apr
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Publications
Massively parallel screen u…
By newseditor
Posted 24 Apr
Distinct genetic and enviro…
By newseditor
Posted 24 Apr
Hippocampus-to-amygdala pat…
By newseditor
Posted 24 Apr
Integrative spatial analysi…
By newseditor
Posted 24 Apr
Time-series reconstruction…
By newseditor
Posted 24 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar