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Devil facial tumour disease (DFTD) comprises two genetically distinct transmissible cancers (DFT1 and DFT2) endangering the survival of the Tasmanian devil (Sarcophilus harrisii) in the wild. DFT1 first arose from a cell of the Schwann cell lineage; however, the tissue-of-origin of the recently discovered DFT2 cancer is unknown. In this study, we compared the transcriptome and proteome of DFT2 tumours to DFT1 and normal Tasmanian devil tissues to determine the tissue-of-origin of the DFT2 cancer. Our findings demonstrate that DFT2 expresses a range of Schwann cell markers and exhibits expression patterns consistent with a similar origin to the DFT1 cancer. Furthermore, DFT2 cells express genes associated with the repair response to peripheral nerve damage. These findings suggest that devils may be predisposed to transmissible cancers of Schwann cell origin. The combined effect of factors such as frequent nerve damage from biting, Schwann cell plasticity and low genetic diversity may allow these cancers to develop on rare occasions. The emergence of two independent transmissible cancers from the same tissue in the Tasmanian devil presents an unprecedented opportunity to gain insight into cancer development, evolution and immune evasion in mammalian species.

Immune checkpoint immunotherapies (ICI) are now approved for over 20 types of cancer and there are almost 6000 ongoing clinical trials investigating immuno-modulators as cancer therapies. This review investigated the effect of monoclonal antibody-based immune checkpoint immunotherapies when combined with cytokine therapy. We reviewed published clinical trial results from 2005 to 2020 for studies that used approved monoclonal antibody ICI in combination with the cytokines. Studies that met the search criteria were assessed for treatment efficacy and immunological changes associated with treatment. ICI often fails to result in improved clinical outcomes for patients and lasting protection from cancer recurrence. The use of pro-inflammatory cytokines alongside ICI has been shown to enhance the efficacy of these therapies in vitro and in animal studies. However, the results in human clinical trials are less clear and many clinical trials do not publish results at the end of the trial. A deeper understanding of the molecular interactions between cytokines, tumors, and immune cells is needed to improve overall ICI outcomes and design combination trials. Critical examination of the design and characteristics of previous clinical trials can provide insight into the lack of effective clinical translation for many immunotherapeutic drugs.