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

Autor:	Flies AS; Menzies Institute for Medical Research, College of Health and Medicine, University of Tasmania, Hobart, TAS 7000, Australia. andy.flies@utas.edu.au., Darby JM; Menzies Institute for Medical Research, College of Health and Medicine, University of Tasmania, Hobart, TAS 7000, Australia., Lennard PR; Menzies Institute for Medical Research, College of Health and Medicine, University of Tasmania, Hobart, TAS 7000, Australia.; The Roslin Institute and Royal School of Veterinary Studies, University of Edinburgh, Easter Bush Campus, Midlothian EH25 9RG, UK., Murphy PR; Menzies Institute for Medical Research, College of Health and Medicine, University of Tasmania, Hobart, TAS 7000, Australia.; University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute, Woolloongabba, QLD, Australia., Ong CEB; Menzies Institute for Medical Research, College of Health and Medicine, University of Tasmania, Hobart, TAS 7000, Australia., Pinfold TL; School of Medicine, College of Health and Medicine, University of Tasmania, Hobart, TAS 7000, Australia., De Luca A; School of Medicine, College of Health and Medicine, University of Tasmania, Hobart, TAS 7000, Australia., Lyons AB; School of Medicine, College of Health and Medicine, University of Tasmania, Hobart, TAS 7000, Australia., Woods GM; Menzies Institute for Medical Research, College of Health and Medicine, University of Tasmania, Hobart, TAS 7000, Australia., Patchett AL; Menzies Institute for Medical Research, College of Health and Medicine, University of Tasmania, Hobart, TAS 7000, Australia.
Jazyk:	angličtina
Zdroj:	Science advances [Sci Adv] 2020 Jul 01; Vol. 6 (27). Date of Electronic Publication: 2020 Jul 01 (Print Publication: 2020).
DOI:	10.1126/sciadv.aba5031
Abstrakt:	Around 40% of humans and Tasmanian devils ( Sarcophilus harrisii ) develop cancer in their lifetime, compared to less than 10% for most species. In addition, 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 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 coexpression of CD200R1 can block CD200 surface expression. The system's versatility across species was demonstrated by fusing a fluorescent reporter to a camelid-derived nanobody that binds human programmed death ligand 1. 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. (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).)
Databáze:	MEDLINE
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