Tasmanian devil CD28 and CTLA4 capture CD80 and CD86 from adjacent cells.

Abstract:

: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.

journal_name

Dev Comp Immunol

authors

Wong C,Darby JM,Murphy PR,Pinfold TL,Lennard PR,Woods GM,Lyons AB,Flies AS

doi

10.1016/j.dci.2020.103882

subject

Has Abstract

pub_date

2021-02-01 00:00:00

pages

103882

eissn

0145-305X

issn

1879-0089

pii

S0145-305X(20)30437-7

journal_volume

115

pub_type

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