Researchers have found that removing a particular enzyme and protein from the immune system significantly reduces the spread of breast cancer and melanoma.
The study was led by QIMR Berghofer Medical Research Institute in collaboration with MedImmune, the global biologics research and development arm of AstraZeneca. It has been published today in the journal Cancer Cell.
Adenosine is an immunosuppressive molecule that promotes the growth and spread of tumours. It does this by sending a message to certain immune cells, which inhibits their ability to kill cancer cells.
Adenosine is made by the enzyme CD73. It sends its messages to immune cells via a protein – known as the A2A adenosine receptor – on the surface of the immune cells.
Researchers from QIMR Berghofer’s Immunology in Cancer and Infection Laboratory wanted to find out the best way to inhibit adenosine to stop it from promoting the growth and spread of cancers.
The laboratory’s Arabella Young said they tested this by inhibiting the enzyme that makes adenosine (CD73) and the protein that receives its messages (the A2A receptor) separately and in combination.
“During our laboratory experiments, targeting the enzyme CD73 and the A2A receptor separately slowed the growth and spread of breast cancer and melanoma,” Ms Young said.
“But when we removed the function of both at the same time, it had a more powerful effect, inhibiting the growth and significantly reducing the spread of the cancers.
“In some of our experiments, removing both CD73 and the A2A receptor eliminated the melanomas altogether.”
A treatment targeting the A2A receptor is currently in clinical trials.
QIMR Berghofer’s Professor Mark Smyth, who led the study, said the Institute’s collaborators at MedImmune had developed another immunotherapy treatment to block CD73 in solid tumours, which is also in clinical trials.
“Removing the enzyme CD73 stops adenosine from being produced and inhibiting the A2A receptor stops adenosine’s message from getting through,” Professor Smyth said.
“Up until now, it was believed that targeting each one individually may have the same effect as targeting the two together, but our results have shown otherwise.
“This is the first time that anyone looked at the effect of targeting CD73 and the A2A receptor together.
“Our findings suggest that targeting both would lead to better results for patients.
“We hope that these findings will in future lead to better treatments for a number of cancers, particularly those with high levels of CD73 and adenosine within the tumour, including triple negative breast cancer, high-grade serous ovarian cancer and melanoma.”