Nav: Home

A genomic barcode tracker for immune cells

July 16, 2019

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.

Rare immune cells that 'see' cancer

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."

Building a cellular barcode tracker

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).

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.

"This high-throughput strategy is really opening the door to a much more detailed understanding of the cellular dynamics of the immune response," says Dr Martin Smith, Leader of the Genomic Technologies Group at Garvan's Kinghorn Centre for Clinical Genomics.

In a proof-of-principle study, the researchers used the method to sample 7,138 cells from the tumour 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 tumour.

A new look at disease

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 behaviour 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.
-end-
This work was funded by The Kinghorn Foundation, The National Breast Cancer Foundation, John & Deborah McMurtrie, The Bill and Patricia Ritchie Foundation, and NHMRC Program Grant 1113904. Study authors Ghamdan Al Eryani, Dr Mandeep Singh, Shaun Carswell and Dr Katherine Jackson recently received the 2019 Palmer Innovation Prize for developing this technique.

Garvan Research Foundation

Related Cancer Articles:

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.
Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.
Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.
More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.
New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.
American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.
Oncotarget: Cancer pioneer employs physics to approach cancer in last research article
In the cover article of Tuesday's issue of Oncotarget, James Frost, MD, PhD, Kenneth Pienta, MD, and the late Donald Coffey, Ph.D., use a theory of physical and biophysical symmetry to derive a new conceptualization of cancer.
Health indicators for newborns of breast cancer survivors may vary by cancer type
In a study published in the International Journal of Cancer, researchers from the UNC Lineberger Comprehensive Cancer Center analyzed health indicators for children born to young breast cancer survivors in North Carolina.
Few women with history of breast cancer and ovarian cancer take a recommended genetic test
More than 80 percent of women living with a history of breast or ovarian cancer at high-risk of having a gene mutation have never taken the test that can detect it.
Radiotherapy for invasive breast cancer increases the risk of second primary lung cancer
East Asian female breast cancer patients receiving radiotherapy have a higher risk of developing second primary lung cancer.
More Cancer News and Cancer Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

Risk
Why do we revere risk-takers, even when their actions terrify us? Why are some better at taking risks than others? This hour, TED speakers explore the alluring, dangerous, and calculated sides of risk. Guests include professional rock climber Alex Honnold, economist Mariana Mazzucato, psychology researcher Kashfia Rahman, structural engineer and bridge designer Ian Firth, and risk intelligence expert Dylan Evans.
Now Playing: Science for the People

#540 Specialize? Or Generalize?
Ever been called a "jack of all trades, master of none"? The world loves to elevate specialists, people who drill deep into a single topic. Those people are great. But there's a place for generalists too, argues David Epstein. Jacks of all trades are often more successful than specialists. And he's got science to back it up. We talk with Epstein about his latest book, "Range: Why Generalists Triumph in a Specialized World".
Now Playing: Radiolab

Dolly Parton's America: Neon Moss
Today on Radiolab, we're bringing you the fourth episode of Jad's special series, Dolly Parton's America. In this episode, Jad goes back up the mountain to visit Dolly's actual Tennessee mountain home, where she tells stories about her first trips out of the holler. Back on the mountaintop, standing under the rain by the Little Pigeon River, the trip triggers memories of Jad's first visit to his father's childhood home, and opens the gateway to dizzying stories of music and migration. Support Radiolab today at Radiolab.org/donate.