We developed tools to study cancer in Tasmanian devils. They could help fight disease in humans

Shutterstock

Andrew S. Flies, University of Tasmania; Amanda L. Patchett, University of Tasmania; Bruce Lyons, University of Tasmania, and Greg Woods, University of Tasmania

Emerging infectious diseases, including COVID-19, usually come from non-human animals. However our understanding of most animals’ immune systems is sadly lacking as there’s a shortfall in research tools for species other than humans and mice.

Our research published today in Science Advances details cutting edge immunology tools we developed to understand cancer in Tasmanian devils. Importantly, these tools can be rapidly modified for use on any animal species.

Our work will help future wildlife conservation efforts, as well as preparedness against potential new diseases in humans.

The fall of the devil

Tasmanian devil populations have undergone a steep decline in recent decades, due to a lethal cancer called devil facial tumour disease (DFTD) first detected in 1996.

A decade after it was discovered, genetic analysis revealed DFT cells are transmitted between devils, usually when they bite each other during mating. A second type of transmissible devil facial tumour (DFT2) was detected in 2014, suggesting devils are prone to developing contagious cancers.

A Tasmanian devil with devil facial tumour disease.
Save the Tasmanian Devil Program

In 2016, researchers reported some wild devils had natural immune responses against DFT1 cancers. A year later an experimental vaccine for the original devil facial tumour (DFT1) was tested in devils artificially inoculated with cancer cells.

While the vaccine didn’t protect them, in some cases subsequent treatments were able to induce tumour regression.

But despite the promising results, and other good news from the field, DFT1 continues to suppress devil populations across most of Tasmania. And DFT2 poses an additional threat.

---

Read more:
Deadly disease can ‘hide’ from a Tasmanian devil’s immune system

---

Following a blueprint requires tools

In humans, there has been incredible progress in treatments targeting protein that regulate our immune system. These treatments work by stimulating the immune system to kill cancer cells.

Our team’s analyses of devil DNA showed these immune genes are also present in devils, meaning we may be able to develop similar treatments to stimulate the devil immune system.

But studying the DNA blueprint for devils takes us only so far. To build a strong house, you need to understand the blueprint and have the right tools. Proteins are the building blocks of life. So to build effective treatments and vaccines for devils we have to study the proteins in their immune system.

Until recently, there were few research tools available for this. And this problem was all too familiar to researchers studying immunology and disease in species other than humans, mice or rats.

Into the FAST lane

You could build a house with just a saw, hammer and nails – but a better and faster build requires a larger, more versatile toolbox.

In our new research, we’ve added more than a dozen tools to the toolbox for understanding tumours in Tasmanian devils. These are Fluorescent Adaptable Simple Theranostic proteins – or simply, FAST proteins.

The term “theranostic” merges therapeutic and diagnostic. FAST proteins can be used as a therapeutic drug to treat a disease, or as a diagnostic tool to determine its cause and better understand it.

A key feature of FAST proteins is they can be tagged with a fluorescent protein marker, and can be released from the cells that we engineered in the lab to make them.

This way, we can collect and observe how the proteins attach and interact with other proteins without needing to add a tag later in the process.

To understand this, imagine trying to use a tiny key in a tiny lock in the dark. It would be difficult, but much easier if both were tagged with a coloured light. In the context of the immune system, it’s easier to understand what we need to turn on or off if we can see where the proteins are.

By mapping how proteins within the devil’s immune system interact, we can find better ways to stimulate the immune system.

An overview of the FAST protein system. Fluorescent proteins and immune system proteins from different species can be rapidly swapped to make new FAST proteins.
Andrew S. Flies/WildImmunity

The FAST system is also adaptable, meaning new targets can be cut-and-pasted into the system as they’re identified, like changing the bits on a drill. Therefore, it’s useful for studying the immune systems of other animals too, including humans.

Also, the system is simple enough that most people with basic cell culture and molecular biology experience could use it.

---

Read more:
A virus is attacking koalas’ genes. But their DNA is fighting back

---

Needle in a haystack

Cancer cells in humans and animals can travel via the bloodstream to spread, or “metastasise”, throughout the body. Identifying single tumour cells in blood can shed light on how cancer invades devils’ organs and kills them.

Using FAST tools, we discovered CD200 – a protein that inhibits anti-cancer responses in humans – is highly expressed in devils. With FAST tools, we were able to mix DFT2 cancer cells into devil blood and pick them out, despite there being about one cancer cell for every 1,000 blood cells.

CD200 is a powerful “off switch” for the immune system, so identifying this off switch allows us it can help us produce a vaccine that disables the switch.

A devil facial tumour 2 (DFT2) cell, with the cell nucleus shown in blue.
Andrew S. Flies/WildImmunity

By rapidly sifting out the best ways to stimulate the devil’s immune system, FAST tools are accelerating our research into developing a preventative vaccine to protect devils from DFT.

Why study animal immune systems?

COVID-19 has once again brought emerging infectious diseases onto the global stage. The ability to rapidly develop immunology tools for new species means we can jump into action when a new virus jumps into humans.

Additionally, species are going extinct at an alarming rate, and wildlife disease is increasingly threatening conservation efforts.

Understanding how the immune systems of other animals fight diseases could provide a blueprint for developing vaccines and therapeutics to help them.

Andrew S. Flies, Senior Research Fellow in Immunology, University of Tasmania; Amanda L. Patchett, , University of Tasmania; Bruce Lyons, , University of Tasmania, and Greg Woods, Professional Research Fellow, University of Tasmania

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Advertisement

Saving the Tasmanian Devil

Sexual aggression key to spread of deadly tumours in Tasmanian devils

Both male and female Tasmanian devils can become very violent during sexual interactions.
Shutterstock/PARFENOV

David Hamilton, University of Tasmania; Elissa Cameron, University of Tasmania; Menna Elizabeth Jones, University of Tasmania, and Rodrigo Hamede, University of Tasmania

Tasmanian devils have a reputation as a fearsome animal – most of the time this is undeserved. When it comes to the mating season, however, it’s a fair judgement. Between February and April, mating can be incredibly aggressive, with male and female devils prone to biting one another both during and after the act.

That could be deadly for the devils, according to new research published online in the journal Behavioral Ecology.

Unfortunately, biting drives the spread of devil facial tumour disease (DFTD) a transmissible cancer that has been afflicting the species since the mid-1990s.

---

Read more:
Survival of the fittest? Perhaps not if you’re a Tasmanian devil

---

DFTD is highly unusual for a cancer because it can transfer between individual devils and grow in its new host.

The fact that devils regularly bite one another around the mouth means tumour cells can easily transfer from an infected devil to an open wound on a healthy devil. This makes the buildup of wounds in devils extremely important to our understanding of this disease.

When devils mate

In our study, we examined the accumulation of bite wounds in a population of wild devils in northwest Tasmania.

We found males were much more likely than females to pick up high numbers of bite wounds. But these wounds appear to be related to the amount of time males spent in mating season interactions with females, as opposed to fights with other males (as we had previously thought).

In the mating season, after male devils have mated with females, they spend an extended period either confining the female in a den, or closely following her to make sure other males are unable to mate with her.

During our study we found this behaviour could go on for up to two weeks in the wild. The process is known as “mate guarding” and is relatively common in the animal kingdom.

We found the longer males spent engaging in mate guarding behaviour, the more bite wounds they received. This would seem to put successful males, who mate with a high number of females, in the firing line when it comes to acquiring DFTD.

But no pattern of sex bias in DFTD prevalence has ever been observed in the wild.

So how does this fit with our study on the increased vulnerability in males?

A Tasmanian devil with the Devil Facial Tumour Disease.
Menna Jones/PLOS ONE, CC BY

Disease transfer

A crucial unknown in the DFTD transmission process involves directionality – which way the deadly disease is passed on by a devil. There are two possibilities:

1. an infected devil bites an uninfected animal, transferring tumour cells (from its teeth or saliva) directly into the wound it causes

2. an uninfected devil bites into tumours on an infected animal, and cells transfer into an open wound inside the biter’s mouth.

The reality is likely to involve a combination of the two.

Our results indicate that most disease transmission occurs during extended mating season interactions, when females appear to be causing high numbers of wounds to their mates.

If DFTD can transfer in either direction during these encounters, then both the males receiving the wounds and the females causing them would be equally at risk of acquiring the disease.

Future of the devil

We have highlighted mating season encounters between the sexes as crucial transmission points for the spread of DFTD. The behaviour of male devils appears to be driving patterns that support transmission of the disease.

This information is important for potential disease management options, as it pinpoints males in good condition – who are likely to be reproductively successful – as targets for management interventions, such as vaccinations.

Most importantly, these results add one more piece to the puzzle of rapid evolution in the Tasmanian devil, in response to the strong evolutionary pressure DFTD is placing on this iconic species. With almost 100% mortality once devils reach breeding age, any advantage an individual devil might have to survive a little longer and reproduce should – over time – spread through the population.

The species has already shown remarkably rapid shifts in their life history and genome, while some are able to mount an immune response and recover from the tumours.

DFTD is spread through biting so we can expect strong evolutionary pressure for devils to become less aggressive towards each other over time.

With these new results, we can now pinpoint for the first time who (healthy, successful males) and when (guarding females after mating) the intense selection pressure on aggressive behaviour in devils will operate.

---

Read more:
Could Tassie devils help control feral cats on the mainland? Fossils say yes

---

Ultimately, devils will solve the DFTD problem themselves by evolving resistance, tolerance and changing their behaviour. One of the best things we can do is let evolution take its course, giving a helping hand along the way via well guided management actions.

David Hamilton, PhD Candidate in Zoology, University of Tasmania; Elissa Cameron, Professor of Wildlife Ecology, University of Tasmania; Menna Elizabeth Jones, Associate Professor in Zoology, University of Tasmania, and Rodrigo Hamede, Post Doctoral Research Fellow, Conservation Biology and Wildlife Management, University of Tasmania

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Could Tassie devils help control feral cats on the mainland? Fossils say yes

The Tasmanian devil once thrived on mainland Australia.
Shutterstock/mastersky

Michael Westaway, Griffith University and Gilbert Price, The University of Queensland

The Tasmanian devil – despite its name – once roamed the mainland of Australia. Returning the devil to the mainland may not only help its threatened status but could help control invasive predators such as feral cats and foxes.

The idea of returning devils to the mainland has been raised before.

---

Read more:
Tasmanian devils reared in captivity show they can thrive in the wild

---

But now we’ve explored the idea from a palaeontological view. We looked at the fossil record of mainland devils, in a paper published online and in print soon in the journal Biological Conservation.

A well preserved devil mandible (lower jaw) recovered from excavations west of Townsville.
Gilbert Price, Author provided

The fossil record helps us better understand how the devils co-existed on mainland Australia with other wildlife. It also helps us see how these iconic animals may possibly interact with small and medium-sized animals if reintroduced to the mainland in the future.

Back in the wild

Ecologists have reintroduced several apex predators to environments where they were once driven to localised extinction. This has helped restore past ecosystems by providing a clearer ecological balance.

One of the best-known examples is the reintroduction of wolves to Yellowstone National Park in the United States, to check the overgrazing and destruction of habitat by elk.

By reintroducing Tasmanian devils into mainland Australia, can we possibly help restore ecological systems that support devils along with small to medium-sized native mammals?

Native and exotic predators

Tasmanian devils and thylacines (Tasmanian tigers) were displaced across the mainland of Australia sometime after the dingo was introduced from southeast Asia at least 3,500 years ago.

But these iconic Australian predators were still able to survive in Tasmania. The island was created 10,000 years ago by rising sea levels, well before the arrival of dingoes on mainland Australia.

Dingoes have now been eradicated across much of mainland Australia, particularly within the seclusion zone of the dingo fence in the southeast of the continent. The 5,400km fence stretches eastwards across South Australia into New South Wales and to southeast Queensland.

Exotic predators such as foxes and cats now thrive across many parts of Australia, and have devastating impacts on small to medium-sized Australian mammals.

But until recently they have not been able to gain a foothold in Tasmania. Many ecologists believe the presence of the devil has prevented these other animals making their destructive mark on the ecology of Tasmania.

Sadly the situation is changing as a result of the deadly devil facial tumour disease, an infectious cancer that has destroyed many populations of Tasmanian devils. Estimates range up to 90% of some population groups now wiped out.

As a result, feral cats are now moving into former devil habitats and hunting native species on Tasmania.

A fossil window to the past

So what does the fossil record tell us about the past life of the Tasmanian devil in mainland Australia?

The Willandra Lakes World Heritage Area, in southeast Australia, provides an extraordinary archaeological and palaeoecological record of Ice Age Australia.

Recovery of fossils and devil coprolites from eroding bettong burrows at the Willandra Lakes World Heritage Area.
Michael Westaway, Author provided

In the past, skeletal remains buried within the landscape were commonly fossilised. Evidence of small animals that dug burrows (such as burrowing bettongs) and the predators that pursued them in their burrows, are exceptionally well preserved.

Our excavations reveal how devils and other small-to-medium sized mammals and reptiles interacted over more than 20,000 years in this area. Even during the peak arid phase, known as the Last Glacial Maximum, it seems that devils and their prey successfully co-existed.

The fossil record (10,000 to 4,000 years ago): This shows the fauna reference condition prior to the arrival of the dingo. (1 Western Quoll, 2 Tasmanian Devil, 3 Thylacine, 4 Bilby, 5 Western Barred Bandicoot, 6 Southern Brown Bandicoot, 7 Burrowing Bettong, 8 Brush Tailed Bettong, 9 Wombat, 10 Nail-Tailed Wallaby, 11 Hare Wallaby, 12 Western and Eastern Grey Kangaroo, 13 Red Kangaroo, 14 Crest Tailed Mulgara, 15 Greater Stick Nest Rat, 16 Hopping Mouse, 17 Fox, 18 Cat, 19 Rabbit)
Toot Toot Design, Author provided

The contemporary record: This shows today’s situation in the Willandra Lakes World Heritage Area. Light grey animals represent those animals that are now locally extinct.
Toot Toot Design, Author provided

The fossil record shows that the range of habitats occupied by devils in the past was far more diverse than today, with populations being found across environments from the central arid core to the northern tropics.

This suggests that devils today should, theoretically, be able to reoccupy a similarly extensive range of habitats.

Former devil range across Australia as revealed by the known fossil record.
Toot Toot Design, Author provided

Better the devil you know

Some ecologists suggest dingoes should be reintroduced into Australian habitats in order to reduce the impact of cats and foxes on native mammals.

One problem is that dingoes also prey on livestock. This is the reason the dingo fence was constructed during the 1880s.

But devils are not active predators of cattle and sheep. So reintroducing a predator that has a much longer evolutionary history with other native mammals in this country would likely receive far less opposition from pastoralists.

---

Read more:
Deadly disease can ‘hide’ from a Tasmanian devil’s immune system

---

A reintroduction of devils back to the mainland may be a new approach to consider for controlling the relentless, destructive march of exotic predators and restore crucial elements of Australia’s biodiversity.

It still needs to be demonstrated that devils can suppress the activities of cats and foxes on the mainland, as they seem to have done in Tasmania. Experiments with devils in a range of different settings would help to establish this.

A new research approach involving palaeontologists, conservation biologists and policy makers may help us understand how we can restore biodiversity function in Australia.

Michael Westaway, Senior Research Fellow, Australian Research Centre for Human Evolution, Griffith University and Gilbert Price, Lecturer in Palaeontology, The University of Queensland

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Tassie devils’ decline has left a feast of carrion for feral cats

Healthy Tasmanian devil populations have cornered the market on carrion.
Menna Elizabeth Jones, Author provided

Calum Cunningham, University of Tasmania; Christopher Johnson, University of Tasmania; Menna Elizabeth Jones, University of Tasmania, and Tracey Hollings, University of Melbourne

The decline of Tasmanian devils is having an unusual knock-on effect: animal carcasses would once have been gobbled up in short order by devils are now taking many days longer to disappear.

We made the discovery, published today in the journal Proceedings of the Royal Society B, by placing carcasses in a range of locations and watching what happened. We found that reduced scavenging by devils results in extra food for less efficient scavengers, such as feral cats.

Tasmanian devils have struggled for two decades against a typically fatal transmissible cancer, called devil facial tumour disease. The disease has caused devil populations to plummet by about 80% on average, and by up to 95% in some areas.

DFTD has spread across most of Tasmania over a 20-year period. Dashed lines show the estimated disease front.
Calum Cunningham/Menna Jones

Scavengers are carnivores that feed on dead animals (carrion). Almost all carnivores scavenge to a greater or lesser degree, but the devil is Tasmania’s dominant scavenger. Since the extinction of the Tasmanian tiger, it is also the island’s top predator.

A scavenging experiment

In our study, we put out carcasses of the Tasmanian pademelon (a small wallaby weighing roughly 5kg) in a variety of places, ranging from disease-free areas with large devil populations, to long-diseased areas where devil numbers are very low. We then used motion-sensor cameras to record all scavenger species that fed on the carcasses.

The Carnivores of Tasmania: a Scavenging Experiment.

Unsurprisingly, much less carrion was consumed by devils in areas where devil populations have declined. This has increased the availability of carrion for other species, such as the invasive feral cat, spotted-tailed quoll, and forest raven. All of these species significantly increased their scavenging in places with fewer devils.

Consumption of experimentally placed carcasses.
Proceedings of the Royal Society B

The responses of native scavengers (quolls and ravens) were subtly different to those of feral cats. The amount of feeding by quolls and ravens depended simply on how much of each carcass had already been consumed by devils. Ravens and quolls are smaller and less efficient than devils at consuming carcasses, so they get the chance to feed only when devils have not already monopolised a carcass.

---

Read more:
Tasmanian devils reared in captivity show they can thrive in the wild

---

In contrast, feral cats tended to scavenge only at sites where devils were at very low abundance. This suggests that healthy devil populations create a “landscape of fear” that causes cats to avoid carcasses altogether in areas where they are likely to encounter a devil. It seems that the life of a feral cat is now less scary in the absence of devils.

Predator prevalence

By looking at 20 years of bird surveys from BirdLife Australia, we also found that the odds of encountering a raven in Tasmania have more than doubled from 1998 to 2017. However, we were unable to directly link this with devil declines. It is likely the raven population is growing in response to a range of factors that includes land-use change and agricultural intensification, as well as reduced competition with devils.

Other studies have shown that cats have also become more abundant in areas where devils have declined. This highlights the potential for devils to act as a natural biological control on cats. Cats are a major threat to small native animals and are implicated in most Australian mammal extinctions.

Carcass concerns

Although smaller scavengers consumed more carrion as devils declined, they were unable to consume them as rapidly as devils. This has resulted in the accumulation of carcasses that would previously have been quickly and completely eaten by devils.

In places with plenty of devils, carcasses were completely eaten within an average of five days, compared with 13 days in places where devil facial tumour disease is rife. That means carcasses last much longer where devils are rare.

DFTD has spread across most of Tasmania over a 20-year period. Dashed lines show the estimated disease front.
Calum Cunningham/Menna Jones

Around 2 million medium-sized animals are killed by vehicles or culled in Tasmania each year, and most are simply left to decompose where they fall. With devils consuming much less carrion, it is likely that carcasses are accumulating across Tasmania. It is unclear how much of a disease risk they pose to wildlife and livestock.

Conserving carnivores

Large carnivores are declining throughout the world, with knock-on effects such as increasing abundance of smaller predators. In recent years, some large carnivores have begun returning to their former ranges, bringing hope that their lost ecological roles may be restored.

Carnivores are declining for many reasons, but an underlying cause is that humans do not necessarily appreciate their pivotal role in the health of entire ecosystems. One way to change this is to recognise the beneficial services they provide.

---

Read more:
Tasmanian devils are evolving rapidly to fight their deadly cancer

---

Our research highlights one of these benefits. It supports arguments that we should help the devil population recover, not just for their own sake but for other species too, including those threatened by feral cats.

The devil seems to be solving the disease problem itself, rapidly evolving resistance to facial tumours. Any management plan will need to help this process, and not hinder it. Potentially, returning devils to mainland Australia could provide similar benefit to wildlife threatened by feral predators.

Calum Cunningham, PhD candidate, University of Tasmania, University of Tasmania; Christopher Johnson, Professor of Wildlife Conservation and ARC Australian Professorial Fellow, University of Tasmania; Menna Elizabeth Jones, Associate professor, University of Tasmania, and Tracey Hollings, Senior Scientist, Ecological Modelling at Arthur Rylah Institute for Environmental Research, and Honorary Research Fellow, University of Melbourne

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Tasmanian Devils in Trouble

Survival of the fittest? Perhaps not if you’re a Tasmanian devil

Aggressive behaviour exhibited by socially dominant Tasmanian devils may predispose them to infection with devil facial tumour disease.
Sebastien Compte/University of Tasmania, Author provided

Konstans Wells, Griffith University; Andrew Storfer, Washington State University; Douglas Kerlin, Griffith University; Hamish McCallum, Griffith University; Menna Elizabeth Jones, University of Tasmania; Paul Hohenlohe, University of Idaho, and Rodrigo Hamede, University of Tasmania

Tasmanian devils in their prime are most likely to become infected with deadly facial tumour disease (DFTD), our research shows.

The findings, published today in Ecology Letters, contradict conventional wisdom that infection of relatively weakened individuals is commonplace in the spread and persistence of diseases.

Instead, it’s the devils that enjoy the highest survival and breeding success who eventually succumb to the fatal disease.

DFTD has had a devastating effect on devil populations in Tasmania, with the marsupial carnivore placed on the endangered list in 2009.

So what is it that makes the fitter devils more prone to infection?

The devils in detail

DFTD is unique in that it is one of only a few known cases of transmissible cancer, where the deadly tumours do not originate from the host body.

The disease is transmitted into an individual when devils bite each other.

To track DFTD in a population, over ten years we repeatedly surveyed more than 500 wild devils, visiting the same field site at least four times per year.

This allowed us to study both survival and reproduction of the devils in the context of infection dynamics and tumour growth.

Our results add to our understanding of how DFTD spreads through devil populations, and reveal more details of how disease-induced evolution in devil populations (such as resistance to the disease) may be occurring.

We suggest the way disease is transmitted plays a key role in who gets infected.

It is the dominant devils who are more likely to engage in aggressive behaviour, such as during mating. This puts them at higher risk of biting an infected individual and thus becoming infected themselves.

So it’s the devils who are otherwise very fit (in the evolutionary sense) that the disease takes out. These are the ones that have the highest survival and reproduction rates, before being killed by the cancer.

Impact on devil populations

So what does this say about the future survival of devil populations in Tasmania’s wild?

Too often, a dramatic-looking disease such as DFTD leaves the impression that it must have detrimental effect on the overall population growth.

But this is not necessarily the case if diseased individuals had a chance to reproduce before they got infected.

Possible scenarios of Tasmanian devil survival and reproduction amid the risk of DFTD infection. The horizontal thick lines indicate individual devil survival over time, small devils reproduction and red dots infestation with tumours.
David Sargent/Queensland College of Art/Griffith University

In the graphic (above) we can see that some devils may not reproduce because either (A) of their social status, or (B) if they get an infection early in life and rapid tumour growth results in death.

In contrast, devils who get the disease late in life © may have already reproduced earlier. In (D) devils may still get infected, but if the tumour grows slowly they may still have chance to reproduce before death.

As for healthy and dominant devils who don’t get the disease (E), they may reproduce several times in their life.

Such details can be vital to understand the spread of DFTD and the outcome for Tasmanian devil populations.

It is the complex interplay of devil demography and disease dynamics that ultimately determines whether DFTD is a conservation threat for devils.

Infection decline

Our results also show a recent decline in the likelihood that devils become infected in this population. This could indicate some evolving resistance of devils to the cancer, as was recently shown by researchers from our team.

Alternatively, the decline in infection rate could have resulted from a reduction in the number of socially dominant devils, if these are responsible for most transmissions of the disease.

If adult devils with high fitness are those that become infected, the potential for selection for resistant animals would be limited.

This is because these individuals still contribute more offspring (and their genetic constitution) to future generations than those not infected and with little engagement in reproduction.

Devil conservation

Our findings could have an impact on some of the conservation strategies for devils, such as vaccination or translocation of devils to other areas.

For example, a targeted vaccination of socially dominant individuals would be more efficient than randomly picking individuals for vaccination.

If devil individuals from captive insurance populations were to be released into wild populations, the consequences for disease spread and population viability would be unpredictable without a better understanding of the role of social behaviour in disease transmission.

If introduced individuals distract existing social structure and more frequently engage in biting behaviour, they may favour the spread of DFTD.

If devils develop resistance to DFTD, the introduction of individuals from captive populations may dilute the natural selection process.

Our study suggest that DFTD appears to be selectively spread and does not affect all individuals in a population. Understanding disease transmission pathways is a prerequisite to aid conservation efforts to stop the spread of unwanted diseases.

Konstans Wells, Research Fellow in Ecology, Griffith University; Andrew Storfer, Professor & Associate Director, School of Biological Sciences, Washington State University; Douglas Kerlin, Postdoctoral Reseach Fellow, Environmental Futures Research Institute, Griffith University; Hamish McCallum, Professor, Griffith School of Environment and Acting Dean of Research, Griffith Sciences, Griffith University; Menna Elizabeth Jones, Associate professor, University of Tasmania; Paul Hohenlohe, , University of Idaho, and Rodrigo Hamede, Post Doctoral Research Fellow, Conservation Biology and Wildlife Management, University of Tasmania

This article was originally published on The Conversation. Read the original article.

Tasmanian Devils in the Barrington Tops

Deadly disease can ‘hide’ from a Tasmanian devil’s immune system

Andrew S. Flies, University of Tasmania and Greg Woods, University of Tasmania

The Tasmanian devil facial tumour (DFT) cells may use a molecular deception – common in human cancers – that could allow the deadly disease to avoid the animal’s immune system, according to our new research published this month.

Recently it was discovered that DFT cells effectively hide from the immune system by not expressing key immune recognition molecules.

Our new discovery that DFT cells contain this “molecular shield” in response to inflammation represents another important step towards understanding the disease and developing more potent ways of preventing or treating it.

So how does this shield work? First, we need to look at some of the recent developments in the treatment of cancers in general.

Cancer treatments

Cancer treatment has undergone a revolution in recent years. Gone are the days when surgery and harsh chemotherapy regimens are the only options.

Now cancer immunotherapy can stimulate the immune system to kill cancer cells. In 2013 this was named the breakthrough of the year in one of the top science journals in the world.

Since 2013 the immunotherapies that target what we call immune checkpoint molecules have continued to make great progress and have recently been approved as first line defences for some cancers.

Checkpoint molecules are critical for keeping the immune system in balance. Every time that the accelerator is pressed in the immune system, there is always at least one, and often several, means of stepping on the brakes.

These checks and balances are necessary because even though the primary job of the immune system is to protect us from disease, the immune system wields powerful weapons that can inflict collateral damage to critical tissues and organ systems when it is aimed at the wrong target.

Programmed death

In recent years the aptly-named checkpoint molecules – “programmed death-1” (PD-1) and “programmed death ligand 1” (PD-L1) – have emerged to be critical regulators of the anti-cancer immune response.

The PD-L1 molecule is used by many types of cancer as a molecular shield to protect the malignant cells from anti-cancer immune responses.

The PD-1 molecule is found on several types of immune cells, but has particular relevance to the anti-cancer responses mediated by T cells.

When PD-1 on a cancer-killing T cell interacts with PD-L1 on cancer cells, the T cell is shut off. The T cell may undergo programmed death or it may linger and play no role in the anti-cancer response.

The worst possibility is that the former cancer-killing T cell hangs around and actually prevents other immune cells from killing cancer cells.

The Tassie devil’s immune system

Our Tasmanian devil immunology team has recently demonstrated that these critical immune checkpoint molecules are also present in devils. This may play a role in the ability of the DFT’s ability to evade the devil immune system.

There likely exists many additional mechanisms that the DFTs use to hide from or suppress the immune system of devils and ongoing research efforts aim to uncover and neutralise these mechanisms.

Recent evidence has shown that some devils have tumour regressions, showing that the tumours are not always able to hide from the immune system.

Spontaneous tumour regression is not common in humans, but it does occur in some people and is likely caused by the immune system recognising and killing tumour cells.

Another deadly disease

But the devils are not out of the woods yet for a few reasons. Only in 2014 a second transmissible cancer (devil facial tumour disease 2 or DFT2) was discovered in wild devils in southern Tasmania.

There are only a handful of naturally transmissible tumours known in the world, so a second transmissible tumour in devils is extremely surprising, like lightning striking the devils twice.

In order for the wild devil population to be truly safe from the transmissible tumours, they would need to have immunity to both the original transmissible tumour DFT and DFT2 and hope that no new transmissible cancers arise.

It remains unknown at this point how many different weapons the tumours use to evade or suppress the immune system.

The tumours themselves can also evolve rapidly in response to ecological and immunological pressure. In many cases, disease causing agents evolve to be less virulent (not kill the animal they infect), but only time will tell if that will happen in the curious case of the devil.

Our ongoing research aims to understand exactly which devil immune system switches can be turned on and off in order to stimulate immune cells to kill cancer cells.

This will be particularly fruitful if we can pinpoint specific genetic and immunological mechanisms that are different in devils that kill tumour cells and those that don’t.

It’s not often that you cheer for the devil, but this is one situation where nearly everybody wants the devil to win!

Andrew S. Flies, Postdoctoral Research Fellow in Immunology, University of Tasmania and Greg Woods, Professional Research Fellow, University of Tasmania

This article was originally published on The Conversation. Read the original article.

Australia: Tasmania – Tasmanian Devils and Feral Cats