A contagious tumour affecting Tasmanian devils – grouchy mammals native to Australia – could offer clues as to why the human immune system can sometimes fail to detect cancer.
Researchers have observed that the Devil Facial Tumour (DFT), a common type of cancer in the marsupials, uses a complex protein mechanism to “hide” from the immune system – the body’s natural defence against disease. This process was also observed in certain human cancers, which prevented the immune system from recognising or attacking cancer cells.
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The international team – which included scientists from the Cambridge Institute for Medical Research, University of Southampton and pharmaceutical company GlaxoSmithKline in the UK working with researchers in Australia – believe their work could pave the way for new drugs for immunotherapy treatments.
Cancer immunotherapy is a form of treatment that uses the body’s own immune system to prevent, control and get rid of the disease. It comes in a variety of forms including targeted antibodies, cancer vaccines and tumour-infecting viruses – and can sometimes treat melanomas and cancers of the lung, kidneys, bladder, bowel, head and neck.
However, in some cases, these cancers can develop resistance to this form of immune attack.
The study, part-funded by Cancer Research UK and published in the journal Cancer Cell, looked at why some cancer cells avoid being detected by the immune system in the first place. The team used cancer cells from human small cell lung cancer, human neuroblastoma (cancer in the nerve tissue), mouse small cell lung cancer and DFT in their experiments.
They found that when a protein complex called PRC2 is overactive, it stops the expression of another protein called MHC class I. The researchers say MHC class I is necessary for the immune system to detect these tumours.
In Tasmanian devils, DFT is spread by biting, causing tumours to form on the face and mouth which are usually fatal. Humans, on the other hand, cannot pass cancer to other people.
However, the researchers believe that the similar “hiding” methods observed in the cancer cells in humans and Tasmanian devils may explain why some cancers respond less well to immunotherapy than others.
Dr Marian Burr, from the Peter MacCallum Cancer Centre in Melbourne and lead study author, said: “We think this could contribute to some cancers in people becoming resistant to immunotherapies, and why cancer cells are not destroyed when transmitted between Tasmanian devils.”
The team suggests a class of drugs called EZH2 inhibitors, which are currently being trialled for a type of blood cancer known as lymphoma, could help avoid evasion. Lab tests showed that MHC class I proteins were restored using EZH2 inhibitors, allowing the immune system to target cancer cells once again.
Prof Mark Dawson, from the Peter MacCallum Cancer Centre, who is senior author on the study, said: “EZH2 inhibitors are showing promising results in clinical trials. So we want to investigate whether they can be combined with immunotherapy treatments, and if they could help patients who don’t respond to immunotherapies alone.”