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dc.contributor.authorYang, Dafeng
dc.contributor.authorJ. Stewart, Trina
dc.contributor.authorKimberly, K.
dc.contributor.authorGeorgi, David
dc.contributor.authorI. Abrams, Scott
dc.contributor.authorLiu, Kebin
dc.date.accessioned2017-05-03T16:13:12Z
dc.date.available2017-05-03T16:13:12Z
dc.date.issued2008
dc.date.modified2013-03-24T22:47:01Z
dc.identifier.issn00207136
dc.identifier.doi10.1002/ijc.23090
dc.identifier.urihttp://hdl.handle.net/10072/49745
dc.description.abstractThe host immune system functions as an intrinsic surveillance network in the recognition and destruction of tumor cells, and it has been demonstrated that lymphocytes and IFN-g are the primary tumor suppressors of the immune system. However, the immune system can concurrently select for tumor variants with reduced immunogenicity and aggressive phenotypes. We report here that tumor escape variants that have survived CTL adoptive immunotherapy exhibited decreased expression levels of both Fas and IFN-gR in vitro. Furthermore, examination of spontaneously arising mouse primary mammary carcinoma and lung metastases revealed that both Fas and IFN-gR protein levels were dramatically lower in lung metastases than in primary tumors in vivo. Functional disruption of either the Fas- or the IFN-g signaling pathway enhanced the colonization efficiency of preexisting metastatic tumor cells, whereas disruption of both Fas and IFN-gR pathways resulted in synergistic augmentation of the colonization efficiency of the preexisting metastatic tumor cells, as determined by experimental lung metastases assay. Gene expression profiling revealed that altered expression of genes involved in immediate IFN-gR signaling, the interferon primary response, apoptosis and tumor colonization is associated with loss of IFN-gR function and enhanced metastatic potential. Interestingly, disruption of IFN-gR function did not alter tumor cell susceptibility to CTL-mediated cytotoxicity, but is linked to enhanced infiltration of endogenous T cells in the tumor microenvironment in vivo. These findings suggest that coordinate downregulation of Fas and IFN-gR, 2 key components of cancer immunosurveillance system on tumor cells, leads to a more aggressive metastatic phenotype.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherJohn Wiley & Sons
dc.publisher.placeUnited States
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom350
dc.relation.ispartofpageto362
dc.relation.ispartofissue2
dc.relation.ispartofjournalInternational Journal of Cancer
dc.relation.ispartofvolume122
dc.rights.retentionY
dc.subject.fieldofresearchCancer Cell Biology
dc.subject.fieldofresearchOncology and Carcinogenesis
dc.subject.fieldofresearchcode111201
dc.subject.fieldofresearchcode1112
dc.titleDownregulation of IFN-γR in association with loss of Fas function is linked to tumor progression
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.date.issued2008
gro.hasfulltextNo Full Text
gro.griffith.authorStewart, Trina


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