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Wednesday May 01, 2019

Contagious Cancer – the curious case of Tasmanian devil facial tumour disease

Summarised by Amanda Oliver & Jessica Borger

We all know that you can’t ‘catch’ cancer from another person, because cancer is not contagious. But, for Tasmanian devils this is not the case.

Native to Tasmania, numbers of Tassie devils have been rapidly declining due to a puzzling type of cancer. Devil facial tumour disease or DFTD originated from a single devil who had developed a facial tumour that had formed from multiplying copies or clones of a single mutated nerve cell. The DFTD tumour cells were transmitted to other devils through open wounds inflicted during feeding and mating when devils savagely fight. Sadly, contracting DFTD is always fatal as painful tumours grow in and around the mouth, face and neck and become infected, leaving the devils unable to eat.

There has been a devastating effect on the numbers of wild Tassie devils, the main predator in Tasmania, since the identification of DFTD in 1996, creating a major environmental problem and costly establishment of conservation programmes. In order to save the wild Tassie devil populations from extinction, scientists have been researching ways to stop the transmission of this deadly disease and eliminate DFTD.

Recently, Gabriella Brown and her colleagues shared their research into DFTD in an article published in Immunology & Cell Biology. In order to understand what these scientists did, first it’s important to understand why it’s peculiar for a cancer to be contagious.

The immune system is designed to protect our body from attack by foreign invaders. To do this the cells in our body carry a unique combination of proteins called antigens. Similar to identifying fingerprints our immune cells can recognise these antigens as ‘self’ and safe. Self antigens are displayed on the surface of cells by a molecule called the major histocompatibility complex (MHC). Foreign invaders that enter our body including viruses, bacteria, microbes and even environmental pollutants are recognised as ‘non-self’ by our immune system as their fingerprints don’t match. When immune cells surveying our body don’t recognise the antigen presented by MHC, they enlist the recruitment of an army of killer T cells to go on the attack and shoot down the enemy with biological warfare. This explains why organ transplants or allografts between humans, who each have cells with their own fingerprints, are often rejected. In a similar way we would expect transmissible or transplanted DFTD allografts to be rejected. So why don’t the Tassie devils reject the tumour cells?

Devils and other marsupials have a similar immune system to humans but in the case of DFTD the killer T cells do not attack the DFTD tumour cells. One way DFTD tumour cells evade detection by the immune system is through camouflage by removing MHC from their surface. Without MHC on the surface of a tumour cell the killer T cells can’t identify the enemy and won’t mount an attack. Luckily, there is another battalion of killer cells, natural killer or NK cells, which search and destroy cells that don’t have any MHC. But in the curious case of DFTD, the Tassie devil’s NK cells fail to mount an attack.

In their study, Dr Brown and colleagues isolated NK cells from the blood of wild Tassie devils and mixed them with DFTD tumour cells in a dish. The DFTD tumour cells survived against the NK cells as they had failed to deploy their weaponry. So did this result mean there was a problem with the ability of the NK cells to seek and destroy?

To address this, 3 different drugs known to switch on NK cells and give them the instruction to attack were tested. When researchers added any one of these drugs to the Tassie devil NK cells to supercharge their killing abilities, they found that the DFTD cells were rapidly destroyed.

This promising result showed that the Tassie devil’s NK cells were fully functional and that instead the DFTD tumour cells have designed a clever evasion strategy to avoid detection or have found a way to overpower the NK cells. NK cells have proteins called inhibitory receptors, which like a brake on a car can be engaged by other cells to stop the killers in their tracks. The addition of any one of the drugs then may have acted like the accelerator pedal.

These fascinating results show that supercharging of NK cells, potentially through vaccination of the Tassie devils with the any of the drugs studied, will instruct the Tassie devil’s immune system to conquer and kill the DFTD tumour cells and one day restore the Tassie devil populations to their former glory.

Read the article in Immunology & Cell Biology