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Key Steps Discovered in Production of Critical Immune Cell

WEHI researchers have uncovered a process cells use to fight off infection and cancer that could pave the way for precision cancer immunotherapy treatment. 

Through gaining a better understanding of how this process works, researchers hope to be able to determine a way of tailoring immunotherapy to better fight cancer.

Led by Dr Dawn Lin and Dr Shalin Naik and published in Nature Cell Biology, the research provides new insight into the way cells adapt to fight infection.

Dr Shalin Naik and Dr Dawn Lin

This research lays the foundation for future studies into the body’s response to environmental stressors, such as injury, infection or cancer, at a single cell level.

At a glance

  • WEHI researchers have studied dendritic cells, a crucial component of the immune system, to gain a deeper understanding of how the body produces these cells to fight cancer and infection
  • The study found how the Flt3L hormone increased dendritic cells numbers
  • Researchers will now apply this knowledge to improving immunotherapy techniques to create more personalised treatments

Flt3L hormone plays vital role in fighting off infection

Dendritic cells are immune cells that activate ‘killer’ T cells, which are vital for clearing viral infections, such as COVID-19, but also for triggering a response to cancers such as melanoma and bowel cancer.

The Flt3L hormone can increase dendritic cell numbers, helping the immune system to fight off cancer and infection.

Dr Naik and his team studied developing immune cells at a single cell level to gain a deeper understanding of how the body uses these cells to trigger immune responses.

“There is one type of dendritic cell that the body uses to fight some infections and cancer. The Flt3L hormone increases numbers of this particular dendritic cell.”   

“We know quite well how the dendritic cell fights the cancer, but we don’t know how the Flt3L hormone increases the numbers of those dendritic cells,” he said  

Single-cell barcoding provides vital clues to how dendritic cells function

Researchers used a single-cell ‘barcoding’ technique to uncover what happened when dendritic cells multiplied.

“By using cellular barcoding – where we insert short synthetic DNA sequences, we call barcodes inside cells – we were able to determine which cells produced dendritic cells in pre-clinical models,” Dr Naik said.

“As a result of this research, we now better understand the actions of the Flt3L hormone that is currently used in cancer immunotherapy trials, and how it naturally helps the body fight cancer and infection. This is a first step to design better precision immunotherapy treatments for cancer.” 

Using single cell technology to improve immunotherapy treatment

This research answers a 50-year-long question as to what causes a stem cell to react in response to immense stress, such as infection or inflammation.

“We have known that the Flt3L hormone increases the number of dendritic cells for decades but now there is a focus on applying this knowledge to cancer immunotherapy and potentially to infection immunotherapy as well,” Dr Naik said.   

“The next stage in our research is to create ‘dendritic cell factories’ using our new knowledge, to produce millions to billions of these infection fighting cells and then use those in immunotherapy treatments.”

“These findings are a vital first step to improving immunotherapy treatments for patients, to help them better fight cancer and infection.”

WEHI authors

Dawn Lin, Luyi Tian, Sara Tomei, Daniela Amann-Zalcenstein, Tracey Baldwin, Tom Weber, Jaring Schreuder, Olivia Stonehouse, Samir Taoudi, Matthew Richie, Philip Hodgkin, Ashley Ng, Stephen Nutt, Shalin Naik.

This article originally appeared on the WEHI website. ACRF has awarded $10m in grants to WEHI for cancer research.

Our esteemed Medical Research Advisory Committee ensures that only the most promising cancer research initiatives in Australia receive our funding. If you would like to financially contribute, please go to acrf.com.au/donate

Researchers expose how ‘James Bond’ cells are made to boost our immune system against cancer.

Our determination to understand how our bodies operate continues to reveal fascinating intricacies.

New research published in the journal of Nature Immunology exemplifies this. In the study, researchers from the ACRF funded Walter and Eliza Hall Institute reveal how immune cell ‘spies’ are created.

These dendritic cells, or ‘James Bond’ cells gather information on disease-causing agents to aid our bodies in fighting them.

“Dendritic cells are the intelligence-gathering cells that educate the immune system,” said Dr Naik from the Walter and Eliza Hall Institute.

“They tell the infection-fighting T cells and NK cells what a virus, bacterium, fungus or cancer looks like so they know what they’re looking for when fighting disease”.

Prior to this discovery, it was thought that dendritic cells shared one ‘parent’. But researchers have found that we actually have an army of unique ‘parent’ cells that decide whether or not to multiply or generate new dendritic cells to help identify and fight disease.

What this new knowledge provides us with are clues on how the immune system could be manipulated to better fight disease. In examining and understanding at a molecular level how our body naturally fights diseases, we can then single out the cells that are doing the right thing and suppress any ‘James Bond’ cells that are aiming at the wrong target.

This discovery could not have been achieved without cutting-edge technology that allows scientists to single out individual immune cells, rather than try to examine thousands at once.

“We and others have been following this family tree from one daughter cell to the next to discover how each cell type is created and how the parent cell ‘decides’ if it should make more of itself or create the next cell type. By dissecting the heritage of these cells, we can find new targets to tackle a range of conditions including infectious diseases, cancers and immune disorders, and even make vaccines more effective,” says Dr Shalin Naik.

Walter and Eliza Hall Institute has received $5.5 million in grants from the ACRF which has funded technology to progress research in lymphoma, breast, lung and genomics.

The original article was published the Walter and Eliza Hall Institute for Medical Research website. To read the original article, please click here.