New potential weapon found in battle against cancer and inflammatory diseases

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QIMR Berghofer-led research has discovered the pivotal role played by an important immune system protein that, if harnessed through immunotherapy, has the potential to treat a wide range of cancers and inflammatory diseases.

The researchers had been working on the tropical parasitic diseases malaria and leishmaniasis when they discovered that the Natural Killer Cell Granule Protein (NKG7) played an important role in a range of diseases.

Professor Christian Engwerda, who is the Acting Head of QIMR Berghofer’s Infectious Diseases program, said his team found that when the NKG7 protein was turned off it reduced inflammation in mice, but if it was stimulated it enhanced the immune response.

“NKG7 is a key promoter of inflammation, which is the basis of many of the diseases we encounter including cancers, autoimmune diseases, neurological diseases and infectious diseases,” Professor Engwerda said.

“The protein was first identified a few decades ago, but no one had worked out that it was a key weapon of the immune system that’s really important for controlling tumours and infections and for helping current medicines work well.

“It does this by delivering the toxic agents from immune cells to targeted disease cells. Our research shows that in cancer, the protein is activated when patients are treated with drugs that switch on the immune system to deliver cancer-killing agents to tumours.

“In autoimmune and other inflammatory diseases where the immune system is overactive, the NKG7 protein is too active, and we found by blocking it in mice, inflammatory damage was reduced.”

The research was conducted in mice and human blood samples collected from leishmaniasis patients in India. The researchers found leishmaniasis patients expressed high levels of the molecule in their blood.

Co-lead author, QIMR Berghofer Senior Scientist and Immunology Department Coordinator, Professor Mark Smyth, said the findings opened the way for new immunotherapies.

“NKG7 is expressed on different immune cells at different stages of disease and our study showed that targeting the protein by blocking its function would be a new way to dampen inflammation in diseases,” he said.

“Activating it on the other hand would enhance the immune response during some infectious diseases and cancer.

“Our research showed some cancer patients who responded well to certain immunotherapies expressed high levels of this molecule in the immune cells attacking their tumours, indicating it can play a role in preventing cancer metastasis.

“The challenge now is to explore what drugs can be used to manipulate the protein in the immune system, so doctors can either turn it on or off, depending on the disease or condition.”

Professor Engwerda said the research demonstrated the value of studying a broad range of diseases, including those that don’t directly affect Australians.

“Apart from it being important for us to play our part as global citizens by trying to find cures for diseases impacting the developing world, this study shows research into any illness can expand our understanding of the immune system and the biology of disease,” he said.

The research was led in collaboration with the Institute of Medical Sciences at Banaras Hindu University in Varanasi, India, as part of a long-standing India-Australia relationship.

The study has been published in the journal Nature Immunology.

The research was partly funded by the National Health and Medical Research Council of Australia, the National Institutes of Health (USA), QIMR Berghofer and the Queensland Government.

 
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