An international team of scientists led by Peter Mac has identified a new way to potentially stop cancer cells hiding from the immune system. Their research has identified a master regulator of a protein (PD-L1) which is over-expressed by tumour cells, and which suppresses the immune response to these rogue cancer cells allowing them to proliferate.
A paper describing this work, titled CMTM6 maintains the expression of PD-L1 and regulates anti-tumour immunity, is published today by the journal Nature.
“For some time we’ve known that PD-L1 plays an important regulatory role for our immune system – and when it is operating normally it is a handbrake that prevents over-reactions,” says Professor Mark Dawson, who is Peter Mac’s Head of the Translational Haematology Program.
“We’ve also know that cancers exploit this process and an over-supply of PD-L1 on the surface of tumour cells effectively shields them, stopping them from being killed off by our immune system.
“If we had a way to control the production of PD-L1 this would be a powerful new addition to our armoury of immunotherapy agents, and that’s what the research has identified.”
The researchers found the protein CMTM6 is needed to maintain the expression of PD-L1 and in a wide variety of cancers cells they showed that as CMTM6 levels decline so does the cancer’s ability to suppress the immune response.
The discovery opens a new avenue to develop immunotherapy drugs that target CMTM6. These would use the similar pathway as emerging “anti-PD1” class of antibody therapies, which have already shown great promise for the treatment of a broad array of cancers, including the spectacular responses of cancer patients such as Jarryd Roughead.
“This is a shining example of what’s possible here in Melbourne’s Parkville precinct - CMTM6 turns out to be the ‘switch’ that enables a cancer to put a brake on the immune system,” says Professor Joe Trapani, Executive Director of Research and Head of the 70-strong Cancer Immunology Program at Peter Mac.
“If we can develop new drugs that re-activate a patient’s immune response to their cancer, this would be a major world-wide advance.
“Immunotherapy is the first totally new treatment for advanced cancer in over 50 years and our capacity for this exciting research project and many more is rapidly expanding.”
The research received funding and collaborative research support from the National Health and Medical Research Council, University of Cambridge, Cancer Research UK, Stanford University in USA, Leukaemia Foundation Australia, Olivia Newton-John Cancer Wellness & Research Centre, Latrobe University and University of Melbourne.