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Lessons learnt from the Tasmanian devil facial tumour regarding immune function in cancer

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Abstract

Genetic and genomic technologies have facilitated a greater understanding of the Tasmanian devil immune system and the origins, evolution and spread of devil facial tumour disease (DFTD). DFTD is a contagious cancer that has caused significant declines in devil populations across Tasmania. Immune responses to DFTD are rarely detected, allowing the cancer to pass between individuals and proliferate unimpeded. Early immunosenscence in devils appears to decrease anti-tumour immunity in older animals compared to younger animals, which may increase susceptibility to DFTD and explain high DFTD prevalence in this age group. Devils also have extremely low major histocompatibility complex (MHC) diversity, and multiple alleles are shared with the tumour, lowering histocompatibility barriers which may have contributed to DFTD evolution. DFTD actively evades immune attack by down-regulating cell-surface MHC I molecules, making it effectively invisible to the immune system. Altered MHC I profiles should activate natural killer (NK) cell anti-tumour responses, but these are absent in DFTD infection. Recent immunisation and immunotherapy using modified DFTD cells has induced an anti-DFTD immune response and regression of DFTD in some devils. Knowledge gained from immune responses to a transmissible cancer in devils will ultimately reveal useful insights into immunity to cancer in humans and other species.

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Acknowledgements

Our work is supported by an Australian Research Council Discovery grant to KB. We thank current and former members of the lab and our collaborators for the significant contributions they have made to this work.

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  1. School of Life and Environmental Science, The University of Sydney, Sydney, NSW, Australia

    Emma Peel & Katherine Belov

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  1. Emma Peel
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Correspondence to Katherine Belov.

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Peel, E., Belov, K. Lessons learnt from the Tasmanian devil facial tumour regarding immune function in cancer. Mamm Genome 29, 731–738 (2018). https://doi.org/10.1007/s00335-018-9782-3

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