Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/23027
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dc.contributor.authorOwen, Katie L-
dc.contributor.authorGearing, Linden J-
dc.contributor.authorZanker, Damien J-
dc.contributor.authorBrockwell, Natasha K-
dc.contributor.authorKhoo, Weng Hua-
dc.contributor.authorRoden, Daniel L-
dc.contributor.authorCmero, Marek-
dc.contributor.authorMangiola, Stefano-
dc.contributor.authorHong, Matthew K-
dc.contributor.authorSpurling, Alex J-
dc.contributor.authorMcDonald, Michelle-
dc.contributor.authorChan, Chia-Ling-
dc.contributor.authorPasam, Anupama-
dc.contributor.authorLyons, Ruth J-
dc.contributor.authorDuivenvoorden, Hendrika M-
dc.contributor.authorRyan, Andrew-
dc.contributor.authorButler, Lisa M-
dc.contributor.authorMariadason, John M-
dc.contributor.authorGiang Phan, Tri-
dc.contributor.authorHayes, Vanessa M-
dc.contributor.authorSandhu, Shahneen-
dc.contributor.authorSwarbrick, Alexander-
dc.contributor.authorCorcoran, Niall M-
dc.contributor.authorHertzog, Paul J-
dc.contributor.authorCroucher, Peter I-
dc.contributor.authorHovens, Chris-
dc.contributor.authorParker, Belinda S-
dc.date2020-04-21-
dc.date.accessioned2020-04-23T04:23:47Z-
dc.date.available2020-04-23T04:23:47Z-
dc.date.issued2020-04-21-
dc.identifier.citationEMBO reports 2020; 21(6): e50162en
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/23027-
dc.description.abstractThe latency associated with bone metastasis emergence in castrate-resistant prostate cancer is attributed to dormancy, a state in which cancer cells persist prior to overt lesion formation. Using single-cell transcriptomics and ex vivo profiling, we have uncovered the critical role of tumor-intrinsic immune signaling in the retention of cancer cell dormancy. We demonstrate that loss of tumor-intrinsic type I IFN occurs in proliferating prostate cancer cells in bone. This loss suppresses tumor immunogenicity and therapeutic response and promotes bone cell activation to drive cancer progression. Restoration of tumor-intrinsic IFN signaling by HDAC inhibition increased tumor cell visibility, promoted long-term antitumor immunity, and blocked cancer growth in bone. Key findings were validated in patients, including loss of tumor-intrinsic IFN signaling and immunogenicity in bone metastases compared to primary tumors. Data herein provide a rationale as to why current immunotherapeutics fail in bone-metastatic prostate cancer, and provide a new therapeutic strategy to overcome the inefficacy of immune-based therapies in solid cancers.en
dc.language.isoeng-
dc.subjectbone metastasisen
dc.subjectdormancyen
dc.subjectimmune evasionen
dc.subjectProstate canceren
dc.subjecttype I interferonen
dc.titleProstate cancer cell-intrinsic interferon signaling regulates dormancy and metastatic outgrowth in bone.en
dc.typeJournal Articleen
dc.identifier.journaltitleEMBO reportsen
dc.identifier.affiliationMurdoch Children's Research Institute, Parkville, Victoria, Australiaen
dc.identifier.affiliationSt Vincent's Clinical School, UNSW Sydney, Sydney, NSW, Australiaen
dc.identifier.affiliationDivision of Bone Biology, Garvan Institute of Medical Research, Sydney, NSW, Australiaen
dc.identifier.affiliationSchool of Biotechnology and Biomolecular Sciences, UNSW Sydney, Sydney, NSW, Australiaen
dc.identifier.affiliationDepartment of Molecular and Translational Science, Monash University, Clayton, Victoria, Australiaen
dc.identifier.affiliationCancer Immunology and Therapeutics Programs, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australiaen
dc.identifier.affiliationTissuePath Specialist Pathology, Mount Waverley, Vic, Australiaen
dc.identifier.affiliationTranslational Research Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australiaen
dc.identifier.affiliationBioinformatics Division, The Walter and Eliza Hall Institute, Parkville, Victoria, Australiaen
dc.identifier.affiliationCancer Research Division, The Kinghorn Cancer Centre/Garvan Institute of Medical Research, Sydney, NSW, Australiaen
dc.identifier.affiliationLa Trobe Institute for Molecular Science, Department of Biochemistry and Genetics, La Trobe University, Melbourne, Victoria, Australiaen
dc.identifier.affiliationCentre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Victoria, Australiaen
dc.identifier.affiliationDepartments of Urology and Surgery, Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australiaen
dc.identifier.affiliationAustralian Prostate Cancer Research Centre Epworth, Richmond, Victoria, Australiaen
dc.identifier.affiliationSir Peter MacCallum, Department of Oncology, University of Melbourne, Parkville, Victoria, Australiaen
dc.identifier.affiliationDepartment of Medical Oncology, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Victoria, Australiaen
dc.identifier.affiliationDepartment of Urology, Frankston Hospital, Frankston, Victoria, Australiaen
dc.identifier.affiliationCentral Clinical School, University of Sydney, Camperdown, NSW, Australiaen
dc.identifier.affiliationGenomics and Epigenetics Division, Garvan Institute of Medical Research, Sydney, NSW, Australiaen
dc.identifier.affiliationDivision of Immunology, Garvan Institute of Medical Research, Sydney, NSW, Australiaen
dc.identifier.affiliationOlivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australiaen
dc.identifier.affiliationFreemason's Foundation Centre for Men's Health, University of Adelaide Medical School, Adelaide, SA, Australiaen
dc.identifier.affiliationSouth Australian Health and Medical Research Institute, Adelaide, SA, Australiaen
dc.identifier.doi10.15252/embr.202050162en
dc.type.contentTexten
dc.identifier.orcid0000-0002-4909-2984en
dc.identifier.orcid0000-0002-8333-1926en
dc.identifier.orcid0000-0001-9123-7684en
dc.identifier.pubmedid32314873-
dc.type.austinJournal Article-
local.name.researcherMariadason, John M
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.fulltextNo Fulltext-
item.grantfulltextnone-
item.languageiso639-1en-
item.openairetypeJournal Article-
crisitem.author.deptOlivia Newton-John Cancer Research Institute-
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