Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/11550
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dc.contributor.authorKnights, Ashley Jen
dc.contributor.authorFucikova, Jitkaen
dc.contributor.authorPasam, Anupamaen
dc.contributor.authorKoernig, Sandraen
dc.contributor.authorCebon, Jonathan Sen
dc.date.accessioned2015-05-16T01:09:51Z
dc.date.available2015-05-16T01:09:51Z
dc.date.issued2012-08-26en
dc.identifier.citationCancer Immunology, Immunotherapy : Cii 2012; 62(2): 321-35en
dc.identifier.govdoc22923192en
dc.identifier.otherPUBMEDen
dc.identifier.urihttp://ahro.austin.org.au/austinjspui/handle/1/11550en
dc.description.abstractInhibitor of apoptosis proteins (IAPs) are critical in regulating apoptosis resistance in cancer. Antagonists of IAPs, such as LCL161, are in clinical development and show promise as anti-cancer agents for solid and hematological cancers, with preliminary data suggesting they may act as immunomodulators. IAP antagonists hypersensitize tumor cells to TNF-α-mediated apoptosis, an effect that may work in synergy with that of cancer vaccines. This study aimed to further investigate the immunomodulatory properties of LCL161 on human immune subsets. T lymphocytes treated with LCL161 demonstrated significantly enhanced cytokine secretion upon activation, with little effect on CD4 and CD8 T-cell survival or proliferation. LCL161 treatment of peripheral blood mononuclear cells significantly enhanced priming of naïve T cells with synthetic peptides in vitro. Myeloid dendritic cells underwent phenotypic maturation upon IAP antagonism and demonstrated a reduced capacity to cross-present a tumor antigen-based vaccine. These effects are potentially mediated through an observed activation of the canonical and non-canonical NF-κB pathways, following IAP antagonism with a resulting upregulation of anti-apoptotic molecules. In conclusion, this study demonstrated the immunomodulatory properties of antagonists at physiologically relevant concentrations and indicates their combination with immunotherapy requires further investigation.en
dc.language.isoenen
dc.subject.otherAntigens, Neoplasm.immunology.pharmacologyen
dc.subject.otherAntineoplastic Agents.pharmacologyen
dc.subject.otherApoptosis.drug effectsen
dc.subject.otherCancer Vaccines.pharmacologyen
dc.subject.otherCells, Cultureden
dc.subject.otherCombined Modality Therapyen
dc.subject.otherCytokines.secretionen
dc.subject.otherDendritic Cells.drug effects.immunologyen
dc.subject.otherHumansen
dc.subject.otherImmunotherapyen
dc.subject.otherInhibitor of Apoptosis Proteins.antagonists & inhibitorsen
dc.subject.otherLeukocytes, Mononuclear.drug effects.immunologyen
dc.subject.otherNF-kappa B.metabolismen
dc.subject.otherPeptides.pharmacologyen
dc.subject.otherT-Lymphocytes.drug effects.immunologyen
dc.subject.otherThiazoles.pharmacologyen
dc.subject.otherUp-Regulation.drug effectsen
dc.titleInhibitor of apoptosis protein (IAP) antagonists demonstrate divergent immunomodulatory properties in human immune subsets with implications for combination therapy.en
dc.typeJournal Articleen
dc.identifier.journaltitleCancer immunology, immunotherapy : CIIen
dc.identifier.affiliationAshley.Knights@ludwig.edu.auen
dc.identifier.affiliationLudwig Institute for Cancer Research Melbourne, Austin Branch, Austin Hospital, 145-163 Studley Road, Heidelberg, VIC, 3084, Australiaen
dc.identifier.doi10.1007/s00262-012-1342-1en
dc.description.pages321-35en
dc.relation.urlhttps://pubmed.ncbi.nlm.nih.gov/22923192en
dc.type.austinJournal Articleen
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.fulltextWith Fulltext-
item.cerifentitytypePublications-
item.grantfulltextopen-
item.languageiso639-1en-
item.openairetypeJournal Article-
crisitem.author.deptOlivia Newton-John Cancer Research Institute-
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