Demonstration of immune responses against devil facial tumour disease in wild Tasmanian devils

Abstract

Devil facial tumour disease (DFTD) is a recently emerged fatal transmissible cancer decimating the wild population of Tasmanian devils (Sarcophilus harrisii). Biting transmits the cancer cells and the tumour develops in the new host as an allograft. The literature reports that immune escape mechanisms employed by DFTD inevitably result in host death. Here we present the first evidence that DFTD regression can occur and that wild devils can mount an immune response against the disease. Of the 52 devils tested, six had serum antibodies against DFTD cells and, in one case, prominent T lymphocyte infiltration in its tumour. Notably, four of the six devils with serum antibody had histories of DFTD regression. The novel demonstration of an immune response against DFTD in wild Tasmanian devils suggests that a proportion of wild devils can produce a protective immune response against naturally acquired DFTD. This has implications for tumour–host coevolution and vaccine development.

PD-L1 Is Not Constitutively Expressed on Tasmanian Devil Facial Tumor Cells but Is Strongly Upregulated in Response to IFN-γ and Can Be Expressed in the Tumor Microenvironment

“…The clonal transmissibility of the DFTs allows for natural serial transfer experiments using cells that have never been cultured in vitro , which could have lasting effects on tumor phenotype, and also facilitates assessment of the roles of PD-1, PD-L1, and PD-L2 in tumor transmission, development, and metastases. Finally, recent evidence suggests that some devils can mount an immune response to DFT tumors (47), and the new reagents developed here could clarify the role of PD-L1 in responders versus non-responders.…”

Infection of the fittest: devil facial tumour disease has greatest effect on individuals with highest reproductive output

“…Third, a small number of individuals are able to mount an immune response and, in some, tumours regress (Pye et al . ). In this context, the implications of our novel results, that is that the otherwise most fit devils become infected, are intriguing.…”

“…), possibly indicating evolution of resistance, as well as evidence of immune responses to DFTD resulting in tumour regressions and recovery after infection (Pye et al . ). Individual heterogeneity in devil behaviour such as physical interaction and biting is another possibility.…”

“…Moreover, recent molecular evidence of a protective immune response of devils against DFTD recorded from our study site (Pye et al . ) suggests that immune responses might impact disease tolerance through regression of tumours. Reconciling these facts with our findings of how population‐level disease dynamics may change over time requires further analysis of how individual‐level heterogeneity in host and tumour genotypes and the behaviour of adult ‘hosts’ and ‘non‐hosts’ drive variation in demographic rates and infection risk and how this translates into population‐level pattern in disease dynamics.…”

Oncogenesis as a Selective Force: Adaptive Evolution in the Face of a Transmissible Cancer

“…However, these epidemiological models were deterministic and did not consider individual differences in phenotypic plasticity, host mortality, susceptibility to infection or the evolution of adaptive responses to DFTD. Recent studies show significant heterogeneities in several of these parameters, suggesting that devils may be able to overcome the extinction threat of DFTD . In this review, we therefore discuss Tasmanian devil genetic and phenotypic traits as well as life history adaptations that could provide the natural ‘tool box’ for the species to overcome the extinction threat of the disease and ensure the survival of this iconic marsupial.…”