Lessons learnt from the Tasmanian devil facial tumour regarding immune function in cancer
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Open Access
Type
ArticleAbstract
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 ...
See moreGenetic 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 downregulating 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 immunization 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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See moreGenetic 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 downregulating 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 immunization 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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Date
2018Source title
Mammalian GenomeVolume
29Publisher
SpringerFunding information
ARC DP180102465Rights statement
This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: http://dx.doi.org/10.1007/s00335-018-9782-3Faculty/School
Faculty of Science, School of Life and Environmental SciencesShare