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A novel system to map protein interactions reveals evolutionarily conserved immune evasion pathways on transmissible cancers


Flies, AS and Darby, JM and Lennard, PR and Murphy, PR and Ong, CEB and Pinfold, TL and De Luca, A and Lyons, AB and Woods, GM and Patchett, AL, A novel system to map protein interactions reveals evolutionarily conserved immune evasion pathways on transmissible cancers, Science Advances, 6, (27) Article eaba5031. ISSN 2375-2548 (2020) [Refereed Article]


Copyright Statement

Copyright 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

DOI: doi:10.1126/sciadv.aba5031


Around 40% of humans and Tasmanian devils (Sarcophilus harrisii) develop cancer in their lifetime, compared to less than 10% for most species. Additionally, devils are affected by two of the three known transmissible cancers in mammals. Immune checkpoint immunotherapy has transformed human medicine, but a lack of species-specific reagents has limited checkpoint immunology in most species. We developed a simple cut-and-paste reagent development system and used the fluorescent fusion protein system to show that immune checkpoint interactions are conserved across 160,000,000 years of evolution, CD200 is highly expressed on transmissible tumor cells, and co-expression of CD200R1 can block CD200 surface expression. The versatility of the system across species was demonstrated by fusing a fluorescent reporter to a well- characterized camelid-derived nanobody that binds human PDL1. The evolutionarily conserved pathways suggest that naturally occurring cancers in devils and other species can be used to advance our understanding of cancer and immunological tolerance.

Item Details

Item Type:Refereed Article
Keywords:Tasmanian devil. facial tumour disease, wild immunology, comparative immunology, immune checkpoint, evolution
Research Division:Biological Sciences
Research Group:Zoology
Research Field:Animal immunology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Flies, AS (Dr Andy Flies)
UTAS Author:Darby, JM (Ms Jocelyn Darby)
UTAS Author:Lennard, PR (Mr Patrick Lennard)
UTAS Author:Murphy, PR (Mr Peter Murphy)
UTAS Author:Ong, CEB (Ms Chrissy Ong)
UTAS Author:Pinfold, TL (Dr Terry Pinfold)
UTAS Author:De Luca, A (Ms Alana De Luca)
UTAS Author:Lyons, AB (Associate Professor Bruce Lyons)
UTAS Author:Woods, GM (Professor Gregory Woods)
UTAS Author:Patchett, AL (Dr Amanda Patchett)
ID Code:139108
Year Published:2020
Funding Support:Australian Research Council (DE180100484)
Web of Science® Times Cited:6
Deposited By:Menzies Institute for Medical Research
Deposited On:2020-05-26
Last Modified:2021-02-15
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