Comparative Analysis of Immune Checkpoint Molecules and Their Potential Role in the Transmissible Tasmanian Devil Facial Tumor Disease

Frontiers in Immunology
Andrew S FliesGregory M Woods

Abstract

Immune checkpoint molecules function as a system of checks and balances that enhance or inhibit immune responses to infectious agents, foreign tissues, and cancerous cells. Immunotherapies that target immune checkpoint molecules, particularly the inhibitory molecules programmed cell death 1 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), have revolutionized human oncology in recent years, yet little is known about these key immune signaling molecules in species other than primates and rodents. The Tasmanian devil facial tumor disease is caused by transmissible cancers that have resulted in a massive decline in the wild Tasmanian devil population. We have recently demonstrated that the inhibitory checkpoint molecule PD-L1 is upregulated on Tasmanian devil (Sarcophilus harrisii) facial tumor cells in response to the interferon-gamma cytokine. As this could play a role in immune evasion by tumor cells, we performed a thorough comparative analysis of checkpoint molecule protein sequences among Tasmanian devils and eight other species. We report that many of the key signaling motifs and ligand-binding sites in the checkpoint molecules are highly conserved across the estimated 162 million years of evolution since the last c...Continue Reading

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Citations

Jan 10, 2018·Frontiers in Immunology·Hugo Amorim Dos Santos de SouzaPaulo Renato Rivas Totino
Sep 27, 2018·Integrative and Comparative Biology·Gregory M WoodsSilvana S Bettiol
Jan 24, 2020·Expert Review of Vaccines·Andrew S FliesRuth J Pye
Jan 5, 2020·Cellular and Molecular Life Sciences : CMLS·Amanda L PatchettGregory M Woods
Jan 22, 2019·Immunological Investigations·Xinying LiHeinrich Körner
Mar 6, 2021·Immunology and Cell Biology·Amanda L PatchettA Bruce Lyons
Apr 3, 2021·Journal of Cancer Research and Clinical Oncology·Chrissie E B OngAndrew S Flies

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Datasets Mentioned

BETA
KY856749
KY856750
KY856751

Methods Mentioned

BETA
RNA-seq
transgenic
PCR

Software Mentioned

cNLS Mapper
VISTA
BLAST
Phobius server
Simple Modular Architecture Research Tool ( SMART )
CLC sequence viewer
Trinity platform
Clustal Omega
VISTA SIQE
RasMol

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