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

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journal contribution
posted on 2023-05-20, 14:31 authored by Andrew FliesAndrew Flies, Jocelyn DarbyJocelyn Darby, Lennard, PR, Murphy, PR, Chrissie OngChrissie Ong, Terry PinfoldTerry Pinfold, Alana De Luca, Alan Lyons, Gregory WoodsGregory Woods, Amanda PatchettAmanda Patchett
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.

Funding

Australian Research Council

History

Publication title

Science Advances

Volume

6

Issue

27

Article number

eaba5031

Number

eaba5031

Pagination

1-13

ISSN

2375-2548

Department/School

Menzies Institute for Medical Research

Publisher

American Association for the Advancement of Science (A A A S)

Place of publication

United States

Rights 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).

Repository Status

  • Open

Socio-economic Objectives

Clinical health not elsewhere classified

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