Australasian Science: Australia's authority on science since 1938

Devilish Epigenetics Drive Tumour

By Stephen Luntz

Tasmanian devil facial tumour disease occurs when epigenetic factors turn off surface molecules that the immune system uses to recognise foreign tissue

, according to research published in the Proceedings of the National Academy of Science. The theory raises several possible routes to a vaccine, but co-author A/Prof Greg Woods says: “None of them are easy”.

Tasmanian devils lack genetic diversity, and it was thought that this was the reason the facial tumour has spread so successfully. However, Woods and others showed in 2011 that devils reject skin grafts from other members of their species (AS, October 2011, p.5), indicating there must be more to the tumour’s success.

The immune system uses the major histocompatibility complex (MHC) to detect foreign tissue. However, the MHC molecules on the surface of tumour cells are turned off. Consequently the immune system sees a cell it cannot distinguish from one of its own.

There has been concern that the disguise is so effective the tumour could get past the immune system of related species, such as quolls, but Woods says: “There needs to be some way for transmission to occur. Devils and quolls interact but they don’t bite each other as much as devils do to other devils.”

Wood thinks devil handlers are probably safe as other aspects of the cancer cell are so alien to humans that our immune system would reject them.

“The MHC genes are methylated to turn them off. If we demethylate or treat them with cytokines we can turn them back on,” says Woods, who admits to being puzzled by how the original switch occurred. While the switch has been reversed in cell cultures, Woods says the interferon-gamma cytokine, which makes the MHC molecules in tumour cells, has such a short life in devils it is problematic to apply.

“One possible solution is to modify the cytokine molecules so they are more stable,” says Woods. Alternative ideas include taking tumour cells from infected devils, modifying them so they express the molecules, and then reinjecting them. “This could jump-start the immune system so it then recognises other tumour cells,” Woods suggests.

The devil’s lack of diversity is still probably a factor in the disease’s spread, preventing the immune system from recognising other aspects of cells beyond the MHC, but Woods says: “The main thing is the tumour’s lack of expression”.