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

View ORCID ProfileAndrew S. Flies, Jocelyn M. Darby, Patrick R. Lennard, Peter R. Murphy, Chrissie E. B. Ong, Terry L. Pinfold, A. Bruce Lyons, Gregory M. Woods, Amanda L. Patchett
doi: https://doi.org/10.1101/831404
Andrew S. Flies
1Menzies Institute for Medical Research, College of Health and Medicine, University of Tasmania, Hobart, TAS 7000, Australia
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  • ORCID record for Andrew S. Flies
  • For correspondence: Andy.Flies@utas.edu.au
Jocelyn M. Darby
1Menzies Institute for Medical Research, College of Health and Medicine, University of Tasmania, Hobart, TAS 7000, Australia
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Patrick R. Lennard
1Menzies Institute for Medical Research, College of Health and Medicine, University of Tasmania, Hobart, TAS 7000, Australia
2The Roslin Institute and Royal School of Veterinary Studies, University of Edinburgh, Easter Bush Campus, Midlothian, EH25 9RG, UK
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Peter R. Murphy
1Menzies Institute for Medical Research, College of Health and Medicine, University of Tasmania, Hobart, TAS 7000, Australia
3University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute, Woolloongabba, Queensland, Australia
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Chrissie E. B. Ong
1Menzies Institute for Medical Research, College of Health and Medicine, University of Tasmania, Hobart, TAS 7000, Australia
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Terry L. Pinfold
4School of Medicine, College of Health and Medicine, University of Tasmania, Hobart, TAS 7000, Australia
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A. Bruce Lyons
4School of Medicine, College of Health and Medicine, University of Tasmania, Hobart, TAS 7000, Australia
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Gregory M. Woods
1Menzies Institute for Medical Research, College of Health and Medicine, University of Tasmania, Hobart, TAS 7000, Australia
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Amanda L. Patchett
1Menzies Institute for Medical Research, College of Health and Medicine, University of Tasmania, Hobart, TAS 7000, Australia
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ABSTRACT

Immune checkpoint immunotherapy has revolutionized medicine, but translational success for new treatments remains low. 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. Unfortunately, little is known about of immune checkpoints in devils and other non-model species, largely due to a lack of species-specific reagents. We developed a simple cut-and-paste reagent development method applicable to any vertebrate species and show that immune checkpoint interactions are conserved across 160 million years of evolution. The inhibitory checkpoint molecule CD200 is highly expressed on devil facial tumor cells. We are the first to demonstrate that co-expression of CD200R1 can block CD200 expression. The evolutionarily conserved pathways suggest that naturally occurring cancers in devils and other species can serve as models for understanding cancer and immunological tolerance.

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GRAPHICAL ABSTRACT

Footnotes

  • Version 2: Figure 6D was updated to state "DFT2" on the x-axis instead of "DFT1" in two locations. Version 3: Title was updated to reflect the broad utility of the FAST proteins system. New Title: A novel system to map protein interactions reveals evolutionarily conserved immune evasion pathways on transmissible cancers

  • https://wildimmunity.com/resources/fast_protein_protocol/

  • https://wildimmunity.com/resources/fast_protein_experiment_templates/

  • https://wildimmunity.com/resources/fast_protein_recipes/

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted January 03, 2020.
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A novel system to map protein interactions reveals evolutionarily conserved immune evasion pathways on transmissible cancers
Andrew S. Flies, Jocelyn M. Darby, Patrick R. Lennard, Peter R. Murphy, Chrissie E. B. Ong, Terry L. Pinfold, A. Bruce Lyons, Gregory M. Woods, Amanda L. Patchett
bioRxiv 831404; doi: https://doi.org/10.1101/831404
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A novel system to map protein interactions reveals evolutionarily conserved immune evasion pathways on transmissible cancers
Andrew S. Flies, Jocelyn M. Darby, Patrick R. Lennard, Peter R. Murphy, Chrissie E. B. Ong, Terry L. Pinfold, A. Bruce Lyons, Gregory M. Woods, Amanda L. Patchett
bioRxiv 831404; doi: https://doi.org/10.1101/831404

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