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


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Flies, AS ORCID: 0000-0002-4550-1859, Darby, JM, Lennard, PR, Murphy, PR, Ong, CEB, Pinfold, TL ORCID: 0000-0002-0506-6389, De Luca, A, Lyons, AB ORCID: 0000-0002-8508-5853, Woods, GM ORCID: 0000-0001-8421-7917 and Patchett, AL ORCID: 0000-0002-8424-4680 2020 , 'A novel system to map protein interactions reveals evolutionarily conserved immune evasion pathways on transmissible cancers' , Science Advances, vol. 6, no. 27 , pp. 1-13 , doi: 10.1126/sciadv.aba5031.

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

Item Type: Article
Authors/Creators: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
Keywords: Tasmanian devil. facial tumour disease, wild immunology, comparative immunology, immune checkpoint, evolution
Journal or Publication Title: Science Advances
Publisher: American Association for the Advancement of Science (A A A S)
ISSN: 2375-2548
DOI / ID Number: 10.1126/sciadv.aba5031
Copyright Information:

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

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