A tale of two tumours: Comparison of the immune escape strategies of contagious cancers☆

The adaptive immune system should prevent cancer cells passing from one individual to another, in much the same way that it protects against pathogens. However, in rare cases cancer cells do not die within a single individual, but successfully pass between individuals, escaping the adaptive immune response and becoming a contagious cancer. There are two naturally occurring contagious cancers, Devil Facial Tumour Disease (DFTD), found in Tasmanian devils, and Canine Transmissible Venereal Tumour (CTVT), found in dogs. Despite sharing an ability to pass as allografts, these cancers have a very different impact on their hosts. While DFTD causes 100% mortality among infected devils and has had a devastating impact on the devil population, CTVT co-exists with its host in a manner that does not usually cause death of the dog. Although immune evasion strategies for CTVT have been defined, why DFTD is not rejected as an allograft is not understood. We have made progress in revealing mechanisms of immune evasion for DFTD both in vitro and in vivo, and here we compare how DFTD and CTVT interact with their respective hosts and avoid rejection. Our findings highlight factors that may be important for the evolution of contagious cancers and cancer more generally. Perhaps most importantly, this work has opened up important areas for future research, including the effect of epigenetic factors on immune escape mechanisms and the basis of a vaccine strategy that may protect Tasmanian devils against DFTD.