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Devil cancer's evasive trick revealed

Evasive tactics A contagious cancer that is pushing the Tasmanian devil to extinction evades the immune system by suppressing important molecules that help identify foreign cells, say researchers.

Devil facial tumour disease is passed between devils when they bite each other. Since 1996 it has spread quickly through the population of the animals, the world's largest remaining marsupial carnivore.

So far, some 90 per cent of devils have been killed by the disease, and experts now say a captive breeding program may be the species' only hope.

The new study, published in the Proceedings of the National Academy of Science, aims to understand why devils' immune systems do not fight off the tumour cells.

"We were trying to understand how it could be that this foreign cell is passing from animal to animal and being invisible to those animal's immune systems," says Kathy Belov, a geneticist from the University of Sydney and a co-author of the study.

Until recently, scientists had thought this was because there was very little genetic diversity among Tasmanian devils. But more recently, scientists have found that even devils that are genetically different to the tumour are also catching the disease, says Belov.

Belov and her colleagues, including Hannah Siddle and Jim Kaufman from the University of Cambridge, focused their attention on an important group of immune system molecules called major histocompatibility (MHC) class I, which are found on the surface of cells.

Immune system flag

MHC molecules help the immune system recognise foreign substances by presenting small fragments of molecules, known as antigens, on the cell surface.

"These molecules are a flag that tells the immune system that something is 'self' or 'non-self'," Belov says. "They're also presenting cancer antigens to the immune system."

Studying devil facial tumour disease cells in the laboratory, the researchers found that certain genes that are required for MHC molecules to be expressed on the cell surface had been suppressed.

"In this paper we show that the tumour has evolved a way to hide from the immune system," Belov says. "By down-regulating MHC, the cell is invisible to the immune system and is not presenting tumour antigens to the immune system."

Using this knowledge, it might be possible in the future to vaccinate Tasmanian devils against the disease by priming their immune systems with tumour cells that do express MHC, the scientists suggest.

The new study may also help scientists better understand human cancers, as this strategy of MHC suppression is repeatedly used by cancer cells.

However the current findings are unlikely to be the whole story of how devil facial tumour disease spreads. As Belov notes, the disease also manages to avoid other parts of the immune system that would normally attack cells without MHC molecules.

"I think it's going to be a lot more complicated than we're saying at this stage."