Devil Facial Tumour 2 (DFT2) is a recently discovered contagious cancer circulating in the Tasmanian devil (Sarcophilus harrisii), a species which already harbours a more widespread contagious cancer, Devil Facial Tumour 1 (DFT1). Here we show that in contrast to DFT1, DFT2 cells express major histocompatibility complex (MHC) class I molecules, demonstrating that loss of MHC is not necessary for the emergence of a contagious cancer. However, the most highly expressed MHC class I alleles in DFT2 cells are common among host devils or non-polymorphic, reducing immunogenicity in a population sharing these alleles. In parallel, MHC class I loss is emerging in vivo, thus DFT2 may be mimicking the evolutionary trajectory of DFT1. Based on these results we propose that contagious cancers may exploit partial histocompatibility between the tumour and host, but that loss of allogeneic antigens could facilitate widespread transmission of DFT2.
eLife digest While cancer cells typically cannot spread between individuals, there are a few examples of contagious tumours. Remarkably, two examples have emerged in a single species, the Tasmanian devil, a marsupial carnivore. These tumours are known as Devil Facial Tumour 1 (or DFT1) and Devil Facial Tumour 2 (or DFT2); both cause tumours round the faces of infected devils. Since it emerged in the 1990s, DFT1 has killed 60–90% of the devil population. Preserving the few remaining healthy devils has been a major challenge for conservationists. This challenge became more urgent in 2014, when the second contagious cancer, DFT2, was discovered circulating in the population. Contagious cancers are rare because the immune system usually eliminates cells coming from outside the body. Each healthy cell carries molecules known as the major histocompatibility complex (MHC) that act as a barcode showing where each cell comes from. The immune system uses these molecules to help it tell the difference between the body’s own cells and those from elsewhere. DFT1 can avoid the immune system and spread to new hosts because it has lost MHC. In 2014, scientists identified a new Tasmanian devil cancer named DFT2, but it was unclear how this second cancer evades the immune system as it spreads from host to host. Caldwell et al. have now examined the MHC on cells from DFT2 cancers, including cells grown in the laboratory and cells taken from cancer biopsies. Biochemical tests showed that the DFT2 cells do carry MHCs, but that the MHC barcodes of DFT2 are similar to those of the devils infected with the disease. This finding may explain how the cancer can spread undetected in these animals, because the immune system does not recognize it as coming from outside the body. Further analyses also reveal that the cancer cells are slowly evolving to lose their MHCs. This means DFT2 could, with time, become as contagious as DFT1. These two contagious cancers threaten the future of the Tasmanian devil. As top predators, devils are key to the ecosystem in Tasmania and their preservation is vital. While DFT2 provides a unique opportunity to study an emerging cancer as it develops, this research will also help to protect the devils and may lead to effective vaccines. These results could also reveal how other cancers avoid the immune system and may help to detect them during treatment. In addition, there are many similarities between contagious cancer cells and organ transplants. Understanding the role of MHC in DFT2 could lead to better ways to prevent rejection following transplants.