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Tasmanian devil CD28 and CTLA4 capture CD80 and CD86 from adjacent cells
journal contribution
posted on 2023-05-20, 19:07 authored by Wong, C, Jocelyn DarbyJocelyn Darby, Murphy, PR, Terry PinfoldTerry Pinfold, Lennard, PR, Gregory WoodsGregory Woods, Alan Lyons, Andrew FliesAndrew FliesImmune checkpoint immunotherapy is a pillar of human oncology treatment with potential for non-human species. The first checkpoint immunotherapy approved for human cancers targeted the CTLA4 protein. CTLA4 can inhibit T cell activation by capturing and internalizing CD80 and CD86 from antigen presenting cells, a process called trans-endocytosis. Similarly, CD28 can capture CD80 and CD86 via trogocytosis and retain the captured ligands on the surface of the CD28-expressing cells. The wild Tasmanian devil (Sarcophilus harrisii) population has declined by 77% due to transmissible cancers that evade immune defenses despite genetic mismatches between the host and tumors. We used a live cell-based assay to demonstrate that devil CTLA4 and CD28 can capture CD80 and CD86. Mutation of evolutionarily conserved motifs in CTLA4 altered functional interactions with CD80 and CD86 in accordance with patterns observed in other species. These results suggest that checkpoint immunotherapies can be translated to evolutionarily divergent species.
History
Publication title
Developmental and Comparative ImmunologyVolume
115Article number
103882Number
103882Pagination
1-7ISSN
0145-305XDepartment/School
Menzies Institute for Medical ResearchPublisher
Pergamon-Elsevier Science LtdPlace of publication
The Boulevard, Langford Lane, Kidlington, Oxford, England, Ox5 1GbRights statement
Copyright 2020 Elsevier LtdRepository Status
- Restricted