Curse of the Devil: Devil Facial Tumour Disease

The world's largest carnivorous marsupial, the Tasmanian devil is facing extinction in the wild due to a transmissible cancer known as Devil Facial Tumour Disease (DFTD). DFTD is a clonal cell line transmitted from host to host with 100% mortality and no known immunity. While it was first considered that low genetic diversity of the population of devils enabled the allograft transmission of DFTD evidence revealed that genetically diverse animals succumb to the disease. Another possibility was that a lack of immunogenicity of the tumour cells could facilitate transmission between devils. To test immunogenicity, mice were injected with viable DFTD cells and anti-DFTD xenograft responses were analysed revealing the cells are immunogenic. However, DFTD cells do not induce an allogeneic response. This is most likely due to an absence of MHC-I expression on the surface of the cells. We discovered devil mononuclear cells can kill DFTD cells in vitro following activation using mitogens and cytokines.  To extend this finding in vivo we used immunodeficient mice as a model of DFTD as these mice engraft the tumour when injected with DFTD cells. The paramount finding was that co-injection of in vitro activated Tasmanian devil mononuclear cells with DFTD cells prevented establishment of DFTD in these mice. Furthermore, now that it is understood that the main mechanism that shield DFTD cells from immunosurveillance is downregulation of MHC-I expression we are now using this mouse model to investigate the possibility of upregulating MHC-I expression within established tumours using immunotherapy.

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