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Publish Date: 
Wednesday, September 2, 2020 - 11:30

Awakening the immune system to fight diseases

Scientists at The Translational Research Institute (TRI) are harnessing the body’s front-line immune cells to fight cancer, with potential new immunotherapies in development.

University of Queensland Diamantina Institute Group Leader, Dr Fernando Guimaraes, heads the Translational Innate Immunotherapy group, behind the new therapeutics. A 2020 Young Tall Poppy Science Award recipient, the Brazilian-born scientist is a recognised world-leader in Natural Killer cell research.

A subset of immune cells, Natural Killer cells, are the rapid, first-line response unit, identifying and killing foreign or abnormal cells in the body.

According to Dr Guimaraes, Natural Killer cells are known for their ability to recognise and target cancer tumour cells, stopping the cells from migrating to other parts of the body. Some cancers, however, have the ability to evade Natural Killer cells.   

“At the heart of all my research is understanding why Natural Killer cells fail to fight some diseases like cancer,” says Dr Guimaraes.

“At the moment, I am working on developing new immunotherapy approaches for diseases that don’t have standard treatments or where existing therapies aren’t effective. Essentially, I want to stimulate the body’s immune system to beat cancer and infectious diseases,” he says.

Cancer cell therapy

Dr Guimaraes has been studying the link between the spread, or metastasis, of cancer cells and the suppression of Natural Killer cells since 2013. His work has led to the discovery of key chemicals produced by diseased tissue microenvironments, which prevent Natural Killer cells from recognising and killing cancer or infected cells.

This breakthrough is paving the way for new treatments that may stop altered cells from “hiding” from Natural Killer cells and spreading, he says.

“Natural Killer cells don’t work as they should in many solid tumours. The role of these cells really has been under-studied and under-appreciated in solid tumours.

“By uncovering some of the key mechanisms that cancer cells use to hijack the killing action of Natural Killer cells, I’ve been able to prove in pre-clinical models that some drugs can restore the Natural Killer cells’ role in the fight against cancer.

“We’ve also developed a computational biology-based screening strategy that identifies which patients would benefit from this therapeutic approach.”

Dr Guimaraes is working towards developing his new anti-cancer therapy, in which patients’ Natural Killer cells will be engineered to kill their cancer cells, and hopes to attract further funding to begin translational studies.

He has also discovered that bacteria and viruses share similar techniques to cancers to progress infection, making his cellular therapy potentially applicable to treating a broad range of different diseases.

Having his laboratory based at TRI is important for the translation of this therapy, says Dr Guimaraes.

“I’m lucky, because TRI is one of the few places in Australia with the clean and good manufacturing practice [GMP] facilities that will allow me to make clinical-grade cellular therapies for use in humans. Having access to this facility will save us years of work,” he says.

Inflammation and autoimmune disease

Dr Guimaraes began his research career studying the role of Natural Killer cells in inflammation. He was the first to discover that these cells are key players in the body’s response to systemic inflammatory response syndrome and sepsis.

He says he is still trying to better understand mechanisms of inflammation through his research program.

“Natural Killer cells are important contributors to the inflammation response used by our immune system, but in some instances that increased inflammation can be detrimental to the individual so it has to be well balanced. There’s still a lot we need to learn so that we can better leverage these cells in fighting infection.”

An unexpected collaboration at the Walter and Eliza Hall Institute (WEHI) in Melbourne led Dr Guimaraes to extend his research to the autoimmune diseases, such as rheumatoid arthritis.

The research team pinpointed natural killer cells as an unexpected source of the inflammatory protein GM-CSF in rheumatoid arthritis, the first clue that these cells contribute to inflammatory autoimmune diseases. The research also explained how GM-CSF signals to other immune cells to prolong joint inflammation, and how GM-CSF signalling to immune cells is kept in check in healthy joints.

These discoveries could indicate potential new therapeutic targets for reducing joint inflammation in rheumatoid arthritis, and could potentially reduce inflammation in other autoimmune disease such as multiple sclerosis.

Basic biology of Natural Killer Cells

Underlying all of the research in Dr Guimaraes team, is a global effort to understand the basic biology of Natural Killer cells. His team is particularly interested in looking at the molecular regulation of the cells in the cell microenvironment.

 “There is so much that we don’t know about what regulate their basic functions. There are lots of potential interventions that we can identify based on that fundamental knowledge,” he says.

“At the moment, we’re looking at different immune suppressive pathways that cancers are most likely using to manipulate and avoid Natural Killer cells. We need to understand how important each pathway might be.”

About Dr Fernando S. F. Guimaraes PhD

Dr Guimaraes completed his undergraduate studies in Brazil, after which he undertook his PhD at the Institute Pasteur (Paris, France). During his PhD, he began his studies into the role of Natural Killer cells in systemic inflammatory response syndrome and sepsis. In 2013, Dr Guimaraes joined the QIMR Berghofer Medical Research Institute in Brisbane as Postdoctoral Fellow. Following this, he was offered a Senior Research Officer position in Professor Nick Huntington’s Immunotherapy Laboratory at WEHI in Melbourne, where he extended his research into the role of Natural Killer cell biology, and development of novel cancer immunotherapy approaches. In September 2019, Dr Guimaraes joined The University of Queensland Diamantina Institute (UQDI) at TRI as a Research Group Leader.

Dr Guimaraes has received funding from the NHMRC, National Breast Cancer Foundation, and Cure Cancer Australia. He is an author on more than 60 papers, and was awarded the 2019 Researcher of the Year by Cure Cancer Australia (2018 runner-up), and more recently the 2020 Science Young Tall Poppy Award.

Research projects

  • Natural Killer cell biology: Study of innate Natural Killer cell lymphocytes from cellular development to function
  • Experimental and translational immunology: Development of novel immunotherapeutic approaches to treat diseases

Recent journal publications

Follow Dr Guimaraes on Twitter: @Fer_NK_nando