Devil Facial Tumour Disease 2

14 November 2018

Interview with

Hannah Siddle, University of Southhampton

In recent years we’ve realised that some cancers can spread - not just around the body but - between individuals. And a very striking example of this is Devil Facial Tumour Disease that’s wiping out the Tasmanian Devil. We think that when these animals fight, cancerous tissue from one can be injected into another by a bite. There it takes root and grows, using an immune trick to prevent it being “rejected” by its new host. Recently, scientists discovered new form of Devil Facial Tumour Disease - DFT2 - distinct from the first one. This hasn’t evolved to hide from the immune system yet, but it if evolves to do that, it could be curtains for the species. Speaking with Chris Smith, Hannah Siddle is studying these diseases at the University of Southampton…

Hannah - Not many people know that some cancers can become transmissible. And what we've been interested in is two transmissible tumours that have occurred in the Tasmanian Devil, which is a marsupial species endemic to the island of Tasmania. And in the mid 1990s a really nasty transmissible tumour emerged called Devil Facial Tumour 1, or DFT-1 and it's had a really negative impact on the population. So, in some areas, 90 per cent of the Devils have actually died. But our most recent work is actually on a more recently emerged contagious cancer in the Tasmanian devil. So this is a species where lightning has kind of struck twice if you like!

Chris - How does the cancer spread from one Tasmanian devil to another?

Hannah - We think that this is actually occurs by biting. Now, this new transmissible tumour DFT-2, which emerged only quite recently, also looks a lot like DFT-1. And actually if you looked at these two tumours, even though they're completely different diseases, they look really similar. So they still cause these huge tumours around the faces of the animals. So with DFT-2, we haven't shown this experimentally but we think that they're also passed by biting.

Chris - It was a number of years ago that Anne-Marie Pearse put some cells from the first of these types of tumours under a microscope and she showed that they had to be clonal: it was exactly the same genetics in each of them. So how did this second type of tumour emerge and how do you know that that's history repeating itself, or as you put it, lightning striking twice?

Hannah - Yeah that's a really good question because actually I mean what you'd kind of assume is that this new tumor would be somehow related to the first tumour, right? That would that would feel more obvious I think, because of how rare these are. But actually, when people first discovered this second tumour and it looked exactly the same, they found that it expressed some proteins on the cell surface of the tumour cells that were different to DFT-1. And then, looking a little bit deeper at the genetics, they found that actually the karyotype or the chromosomes of this new tumor were really different to DFT-1, the first tumour, and then going even deeper and looking at some of the specific genetic markers they were different as well, and they were also different to the host animals. So, from this it's really clear that this new tumour actually emerged in a completely independent animal - so a completely different animal - that came from a different part of Tasmania and lived much more recently.

Chris - One of the first things that you published on this was the discovery as to why, when you put foreign tissue from one of these animals into another animal, the immune system doesn't recognise it and get rid of it. Why is that?

Hannah - Yeah. So initially when we were looking at this disease in Tasmanian devils, there was... we thought that it was just because they had low genetic diversity, and that's why we could have these cells grafting if you like as a graft between them because we know in humans and mice that you can't just take skin cells skin or a kidney and transplant it to someone else it just doesn't work. The immune system sees it and it rejects it. And what we were able to show with the first tumour is that the tumour cells have down-regulated or lost really important molecules from the cell surface which are called MHC Class 1 molecules; and the tumour has cleverly lost these to make it invisible to a certain subset of immune cells are called T cells. And so that's how DFT-1 really probably became so dangerous and managed to kill so many devils.

Chris - It flies under the immune radar?

Hannah - Yes that's right. Yes.

Chris - Does the second type that you're now describing pull the same stunt?

Hannah - Yes. So that's... that's what we were asking the question in this paper. And as so often happens in science you start out answering one question and actually you end up answering something different. But we did manage to answer that first question and to our surprise, the second tumour DFT-2 still expressed MHC Class 1. So how is it possibly moving between individuals? And I don't think in this paper that with being able to conclude this 100 per cent. But what we've proposed based on our results is that actually the tumour and the host animals that are within that population actually share a lot of their MHC Class 1 molecules. So in the human population you have so much - what we call - diversity, genetic diversity in these molecules that you can't do transplants. But we think that perhaps this tumour has kind of stayed at the moment within its like favourite animals that have very similar MHC molecules to what it has.

Chris - it's sort of showing us how dirty one could have evolved in the first place it could have started out a bit like this and then evolved to have this this down regulation of the immune response. This one is now doing the same thing?

Hannah - Yes. And if that's right we're really concerned about how quickly the new tumour could spread, because if the fact that it has expressed MHC Class 1 has kind of held it back or kept it in it in a constrained population, if it loses MHC Class 1 presumably those constraints are off and it could really spread and transmit much more easily. And from what we know at the moment it seems as if it is just as aggressive - in terms of killing the animals - as DFT-1. And unfortunately though we have far fewer devils; they have less genetic diversity than they did 20 years ago before they got in any of these diseases. So we have a much more vulnerable species.

Chris - And looking on the bright side, does what you've discovered shed any light on how we might better stop this thing?

Hannah - Hmm. Yeah that's kind of the million dollar question isn't it? And I wish I had a better answer to that. One thing that my lab is working on is trying to design better vaccine strategies against this. And you know that is a pretty tall order, but we have had some success against DFT-1 that still needs more work but that does look as if it's promising. And I think, at the moment though, it's really getting a better understanding of these tumours because if you think about it if we didn't even know that these tumours were losing MHC Class 1 we might be quite complacent that this tumour was just going to stay confined to these animals. So really understanding - and I think that's a general lesson isn't it - the more we understand about how diseases and pathogens work then you know the more chance we have of being able to come up with ways of preventing them spreading further...

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