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dc.contributor.authorFlies, AS
dc.contributor.authorLyons, AB
dc.contributor.authorCorcoran, LM
dc.contributor.authorPapenfuss, AT
dc.contributor.authorMurphy, JM
dc.contributor.authorKnowles, GW
dc.contributor.authorWoods, GM
dc.contributor.authorHayball, JD
dc.date.accessioned2020-12-22T03:16:45Z
dc.date.available2020-12-22T03:16:45Z
dc.date.issued2016-12-09
dc.identifier.citationFlies, A. S., Lyons, A. B., Corcoran, L. M., Papenfuss, A. T., Murphy, J. M., Knowles, G. W., Woods, G. M. & Hayball, J. D. (2016). PD-L1 Is Not Constitutively Expressed on Tasmanian Devil Facial Tumor Cells but Is Strongly Upregulated in Response to IFN-gamma and Can Be Expressed in the Tumor Microenvironment. FRONTIERS IN IMMUNOLOGY, 7 (DEC), https://doi.org/10.3389/fimmu.2016.00581.
dc.identifier.issn1664-3224
dc.identifier.urihttp://hdl.handle.net/11343/257817
dc.description.abstractThe devil facial tumor disease (DFTD) is caused by clonal transmissible cancers that have led to a catastrophic decline in the wild Tasmanian devil (Sarcophilus harrisii) population. The first transmissible tumor, now termed devil facial tumor 1 (DFT1), was first discovered in 1996 and has been continually transmitted to new hosts for at least 20 years. In 2015, a second transmissible cancer [devil facial tumor 2 (DFT2)] was discovered in wild devils, and the DFT2 is genetically distinct and independent from the DFT1. Despite the estimated 136,559 base pair substitutions and 14,647 insertions/deletions in the DFT1 genome as compared to two normal devil reference genomes, the allograft tumors are not rejected by the host immune system. Additionally, genome sequencing of two sub-strains of DFT1 detected greater than 15,000 single-base substitutions that were found in only one of the DFT1 sub-strains, demonstrating the transmissible tumors are evolving and that generation of neoantigens is likely ongoing. Recent evidence in human clinical trials suggests that blocking PD-1:PD-L1 interactions promotes antitumor immune responses and is most effective in cancers with a high number of mutations. We hypothesized that DFTD cells could exploit the PD-1:PD-L1 inhibitory pathway to evade antitumor immune responses. We developed recombinant proteins and monoclonal antibodies (mAbs) to provide the first demonstration that PD-1 binds to both PD-L1 and PD-L2 in a non-placental mammal and show that PD-L1 is upregulated in DFTD cells in response to IFN-γ. Immunohistochemistry showed that PD-L1 is rarely expressed in primary tumor masses, but low numbers of PD-L1+ non-tumor cells were detected in the microenvironment of several metastatic tumors. Importantly, in vitro testing suggests that PD-1 binding to PD-L1 and PD-L2 can be blocked by mAbs, which could be critical to understanding how the DFT allografts evade the immune system.
dc.languageEnglish
dc.publisherFRONTIERS MEDIA SA
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titlePD-L1 Is Not Constitutively Expressed on Tasmanian Devil Facial Tumor Cells but Is Strongly Upregulated in Response to IFN-gamma and Can Be Expressed in the Tumor Microenvironment
dc.typeJournal Article
dc.identifier.doi10.3389/fimmu.2016.00581
melbourne.affiliation.departmentMedical Biology (W.E.H.I.)
melbourne.source.titleFrontiers in Immunology
melbourne.source.volume7
melbourne.source.issueDEC
dc.rights.licenseCC BY
melbourne.elementsid1177492
melbourne.contributor.authorMurphy, James
melbourne.contributor.authorCorcoran, Lynn
melbourne.contributor.authorPapenfuss, Anthony
dc.identifier.eissn1664-3224
melbourne.accessrightsOpen Access


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