Immune 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.

Item Type:	Refereed Article
Keywords:	immune checkpoint, wild immunology, transmissible cancer, trans-endocytosis, trogocytosis, intercellular protein transfer
Research Division:	Biological Sciences
Research Group:	Zoology
Research Field:	Animal immunology
Objective Division:	Health
Objective Group:	Clinical health
Objective Field:	Clinical health not elsewhere classified
UTAS Author:	Wong, C (Ms Candida Wong)
UTAS Author:	Darby, JM (Ms Jocelyn Darby)
UTAS Author:	Murphy, PR (Mr Peter Murphy)
UTAS Author:	Pinfold, TL (Dr Terry Pinfold)
UTAS Author:	Woods, GM (Professor Gregory Woods)
UTAS Author:	Lyons, AB (Associate Professor Bruce Lyons)
UTAS Author:	Flies, AS (Dr Andy Flies)
ID Code:	141670
Year Published:	2021
Deposited By:	Menzies Institute for Medical Research
Deposited On:	2020-11-09
Last Modified:	2021-02-15
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