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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

Microscopic behaviour of developing breast cells uncovered

An improved high-tech fluorescence microscopy technique is allowing researchers to film cells inside the breast as never seen before.

This new protocol provides detailed instructions on how to capture hi-res movies of cell movement, division and cooperation, in hard-to-reach regions of breast tissue.

The technology – called multiphoton microscopy – uses infrared lasers to illuminate fluorescently labelled breast cells without harming them, so that elusive cell behaviours can be observed within living tissue.

With the new method, WEHI researchers have revealed how breast cells rearrange, interact and sense their environment as the breast grows during development and recedes after lactation.

Cell imaging within living tissue has been achieved in many organs but the breast has remained especially challenging. So far, this new method has revealed exciting and unexpected details of breast biology and will help teams worldwide to advance research on breast development and cancer.

At a glance

An improved imaging protocol is allowing researchers to film cells as never seen before.

This new application of high-tech microscopy has enabled the imaging of stem cells as they guide breast development, and immune cells as they monitor the breast ducts to keep them healthy.

By imaging living, moving cells in their natural setting, researchers can better understand how our bodies function in real-time at the microscopic scale.


Understanding cell function

The protocol was developed by researcher Dr Caleb Dawson, in a team led by Professor Jane Visvader and Dr Anne Rios, in collaboration with Dr Scott Mueller from the Doherty Institute, and published in Nature Protocols today.

Dr Dawson said the filming technique unlocked a variety of applications to better understand how cells function, interact and develop.

“One of the most valuable things we have been able to film with the technique are the terminal end buds (TEBs) in breast tissue,” he said.

“These are club-like structures at the tips of the mammary ducts that grow during puberty to produce the branched tree structure of breast tissue. The unique cells inside the TEBs have never been filmed like this before so it was fascinating to watch this process for the first time.”

“We have watched a cell behaviour inside the TEB that was hypothesised in the 1980s but was never proven, and which has implications for breast stem cell function.”


Previously, TEBs had been studied by dissociating the individual cells and filming them outside the breast or by taking still images. With these approaches it is difficult to know how the cells actually behave and interact in living tissue.

“By filming the moving cells inside intact breast tissue in laboratory models, we are able to grasp a better understanding of how the cells behave and cooperate to help the breast to form and function properly.”

Dr Dawson said that he was grateful for the brilliant team and the cutting-edge technology provided by the Center for Dynamic Imaging at WEHI that made this work possible.

“When we embarked on our mission to film these processes, I had little knowledge of the effort it would require. With the vision of leading breast researchers Professor Visvader, Dr Rios and Professor Geoff Lindeman, alongside the live imaging expertise of Dr Mueller, and the microscopes available, we were able to achieve something that very few labs in the world have accomplished,” he said.

Opening the doors to new research opportunities

Dr Dawson said the filming technique could be applied to a host of research endeavours.

“Our approach enables us to image up to six fluorescent colours at the same time, which allows us to see how more cell types interact,” he said.

“We can image different stages of breast development, immune cells, lymph nodes and hair follicles and watch how individually-labelled cells function.”

“This means we can create beautiful images with extremely fine details about the cell shapes to get a better understanding of how cells interact and change over time. This opens up many new research opportunities and we are only just starting to see the potential of what this could be used for.”

Dr Dawson said he hoped the imaging protocol would make this type of imaging more widely accessible to researchers.

“There are very few research institutions doing this really high-end imaging, so it is great that we have this capacity in Melbourne and can share it with research teams worldwide.”

The original news article was posted on the WEHI website. Video courtesy of WEHI.

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

Cancer patients could benefit from blood disorder treatment

Cancer scientists at the Walter and Eliza Hall Institute (WEHI) have recently discovered an existing treatment for a blood disorder could potentially also treat stomach and bowel cancer – two of the most common cancers worldwide.

Pre-clinical trials have found an existing class of medicines called ‘JAK inhibitors’ reduce the growth of inflammation often associated with stomach and bowel cancer.

JAK inhibitors are currently being used to treat myelofibrosis and are currently in clinical trials for the treatment of other conditions such as leukaemia, lymphoma, lupus and rheumatoid arthritis.

By understanding the way molecules are involved in promoting the survival and growth of cancer cells, researchers have been able to identify which of these molecules can be targeted with potential anti-cancer treatments.

The research team at WEHI discovered that certain types of bowel and stomach cancer were influenced by proteins, called JAKs, which helped with the cancer growth and formation.

Dr Emma Stuart, Dr Tracy Putoczki and Associate Professor Matthias Ernst from the WEHI made this discovery.

“It was exciting to discover that when JAKs were blocked with existing medications (JAK inhibitors), bowel and stomach cancer growth in experimental models was slowed, and many of the cancer cells were killed,” Dr Stuart said.

The discovery of JAK inhibitors has stemmed from research into the links between inflammation and cancers of the digestive tract.

“Recently we have begun to unravel the complex signalling that occurs in inflamed tissues, such as when a person has a stomach ulcer or suffers from inflammatory bowel disease, and how this drives cancer development,” said Dr Stuart.

This discovery of a treatment that already exists which can be safely and successfully inhibited in patients is very promising.

The Australian Cancer Research Foundation is dedicated to funding research which leads to better treatment outcomes for all types of cancer, and we are proud to have provided millions of dollars in funding to the team of researchers working at Melbourne’s WEHI.

These findings have been published in the journal Molecular Cancer Therapeutics.

Existing blood disorder medicine shows promise in treating certain stomach and bowel cancers

Cancer scientists at the Walter and Eliza Hall Institute (WEHI) have recently discovered an existing treatment for a blood disorder could potentially also treat stomach and bowel cancer – two of the most common cancers worldwide.

Pre-clinical trials have found an existing class of medicines called ‘JAK inhibitors’ reduce the growth of inflammation often associated with stomach and bowel cancer.

JAK inhibitors are currently being used to treat myelofibrosis and are currently in clinical trials for the treatment of other conditions such as leukaemia, lymphoma, lupus and rheumatoid arthritis.

Continue reading “Existing blood disorder medicine shows promise in treating certain stomach and bowel cancers”

70% of cancer patients have new hope through WEHI discovery

A discovery led by Australian researchers at Melbourne’s Walter and Eliza Hall Institute (WEHI) has given new hope to those suffering from certain types of lymphomas as well as other types of blood cancers and some solid tumours.

For these types of cancers, which are driven by a cancer-causing protein, ‘MYC’, Dr Gemma Kelly, Dr Marco Herold, Professor Andreas Strasser and their research team at WEHI have uncovered a promising treatment strategy.

MYC affects up to 70 per cent of human cancers, including many leukaemias and lymphomas. It is responsible for cancerous changes in cells by forcing them into abnormally rapid growth. But the WEHI research team have discovered that MYC activity is co-dependent on another protein, called MCL-1.

Continue reading “70% of cancer patients have new hope through WEHI discovery”

Unprecedented success in trialling new adult leukaemia therapy

A new, potentially life-saving drug has raised new hope for patients in advanced stages of chronic lymphocytic leukaemia – one of the most common types of adult leukaemia in Australia.

In many cases this cancer becomes resistant to traditional treatment methods such as chemotherapy. This is because of its high levels of a “pro-survival” protein called BCL-2 that render cancer cells, according to Walter and Eliza Hall Institute haematologist Prof. Andrew Roberts “basically indestructible”.

Continue reading “Unprecedented success in trialling new adult leukaemia therapy”

Research news: spring 2013

In the spring edition of the Research Review:

  • Research advances building precision tools for diagnosis and cancer surgery.
  • Breast cancer treatment could be enhanced with an existing anti-leukaemia compound.
  • ‘Junk’ DNA and its role in cell growth and development

 

 

WEHI researchers identify an exciting new approach to the treatment of stomach and bowel cancers

Melbourne researchers from the Walter and Eliza Hall Institute (WEHI) have identified a potential new drug target (a molecule called interleukin-11) for the treatment of bowel and stomach cancer, which are two of the most common cancers worldwide.

When a tumour develops in the stomach or bowel region, the normal (non-cancerous) tissues around it often becomes inflamed producing many different molecules, including two particular (related) cytokine molecules: interleukin-11 and interleukin-6.

Interleukin-6 has long been in the spotlight in terms of cancer research, as it is known to promote the spread of cancer cells. In fact, anti-cancer agents that block interleukin-6 are already in clinical trials for ovarian, kidney, prostate and breast cancers.

However, interleukin-11 has only been thought to have a minor role in the growth and spread of cancers. Continue reading “WEHI researchers identify an exciting new approach to the treatment of stomach and bowel cancers”

Treatment for breast cancer enhanced with anti-Leukaemia compound

WEHI image Profs Visvader, Lindeman, and HuangMore than two decades of research at the Walter and Eliza Hall institute (WEHI) in Melbourne has culminated in a potentially life-saving discovery for women with the most common form of breast cancer.

In the late 1980s scientists at the WEHI identified a “pro-survival” protein called BCL-2 that helps cancer cells to become immortal and resist treatments such as chemotherapy. This work has contributed to the development of a compound which neutralises this vital cancer protein, and it is now in clinical trials to treat some types of leukaemia.

But latest news from the WEHI is that this compound has even more potential.

In 85% of women with oestrogen receptor-positive (or ER-positive) breast cancer, researchers have found very high levels of the very same BCL-2 protein.

Using the world-class facilities made possible through ACRF funding they were able to trial this ant-cancer compound in pre-clinical ER-positive breast cancer models, and found that it was successful when combined with an existing breast cancer drug, Tamoxifen. Continue reading “Treatment for breast cancer enhanced with anti-Leukaemia compound”

Discovery brings hope for new tailor-made anti-cancer agents

Researchers at the Walter and Eliza Hall Institute (WEHI) Melbourne have played a key role in developing a novel chemical compound which blocks a protein that has been linked to poor treatment responses in cancer patients.

The development of this compound is an important step towards designing a potential new anti-cancer agent, which will help to significantly reduce resistance to therapy.

The compound targets the function of a protein which prevents cells from dying.

Cell death is an important safeguard against cancer development, but once cancer cells start growing, they can produce high levels of this protein which prevents this natural process. This also reduces the effectiveness of chemotherapy and other anti-cancer treatments, and has been associated particularly with poorer outcomes in patients with lung, stomach, colon and pancreatic cancer.

Dr Guillaume Lessen (pictured) who co-led the study, together with Prof. Keith Watson and Prof. David Huang from the ACRF Chemical Biology Division at WEHI and colleagues Dr Peter Czabotar and Prof. Peter Colman, said:

“We were very excited to see the team’s work culminate in a compound that specifically inhibits the protein.” Continue reading “Discovery brings hope for new tailor-made anti-cancer agents”

Congratulations to ACRF medical research advisor, Professor Doug Hilton

Director of the Walter and Eliza Hall Institute of Medical Research, Professor Douglas Hilton has been awarded the Milstein Award in Florence, Italy.

The Milstein Award is considered to be the pinnacle of scientific achievement in interferon and cytokine research, which involves the study of the immune system and cell communication.

We congratulate Professor Hilton on this most prestigious award and thank him for his contributions to cancer research. Continue reading “Congratulations to ACRF medical research advisor, Professor Doug Hilton”

Breast cancer stem cell discovery follows $5 million grant from ACRF

walter_eliza_building1Scientists at the Walter & Eliza Hall Institute (WEHI) are now able to explain the links between breast cancer risk and exposure to female hormones, paving the way for breast cancer preventions and treatments.

The research, led by Dr Jane Visvader and Dr Geoff Lindeman, was partially supported by a $5 million grant from the Australian Cancer Research Foundation (ACRF). The new discovery was published in the international journal Nature on 12 April 2010.

The research team at the Institute discovered that breast stem cells, despite lacking receptors for oestrogen and progesterone, are still extra sensitive to sustain exposure to the female hormones oestrogen and progesterone. Continue reading “Breast cancer stem cell discovery follows $5 million grant from ACRF”

Spreading the load of cancer research

The influence and support of the Australian Cancer Research Foundation (ACRF) is set to spread further with the news that three of the four major cancer research centres in the running for support this year have made the cut for the first time.

All of the centres involved are on the list of qualifiers for ACRF’S multi-million dollar annual funding program which supports projects which will have a global impact on cancer research.

The three new finalists are The Children’s Medical Research Institute (CMRI) with University of Newcastle NSW, The Kolling Institute of Medical Research, Sydney and the Centre For Cancer Biology South Australian Pathology and the University of Adelaide.

A fourth organisation, the Walter and Eliza Hall Institute Melbourne (WEHI), which in the past has received more than $6 million in two successful grant applications in both 2002 and 2006, is also up for consideration.

Continue reading “Spreading the load of cancer research”