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dc.contributor.authorTakeda, K
dc.contributor.authorNakayama, M
dc.contributor.authorHayakawa, Y
dc.contributor.authorKojima, Y
dc.contributor.authorIkeda, H
dc.contributor.authorImai, N
dc.contributor.authorOgasawara, K
dc.contributor.authorOkumura, K
dc.contributor.authorThomas, DM
dc.contributor.authorSmyth, MJ
dc.date.accessioned2020-12-22T05:02:06Z
dc.date.available2020-12-22T05:02:06Z
dc.date.issued2017-02-24
dc.identifierpii: ncomms14607
dc.identifier.citationTakeda, K., Nakayama, M., Hayakawa, Y., Kojima, Y., Ikeda, H., Imai, N., Ogasawara, K., Okumura, K., Thomas, D. M. & Smyth, M. J. (2017). IFN-gamma is required for cytotoxic T cell-dependent cancer genome immunoediting. NATURE COMMUNICATIONS, 8 (1), https://doi.org/10.1038/ncomms14607.
dc.identifier.issn2041-1723
dc.identifier.urihttp://hdl.handle.net/11343/258195
dc.description.abstractGenetic evolution that occurs during cancer progression enables tumour heterogeneity, thereby fostering tumour adaptation, therapeutic resistance and metastatic potential. Immune responses are known to select (immunoedit) tumour cells displaying immunoevasive properties. Here we address the role of IFN-γ in mediating the immunoediting process. We observe that, in several mouse tumour models such as HA-expressing 4T1 mammary carcinoma cells, OVA-expressing EG7 lymphoma cells and CMS5 MCA-induced fibrosarcoma cells naturally expressing mutated extracellular signal-regulated kinase (ERK) antigen, the action of antigen-specific cytotoxic T cell (CTL) in vivo results in the emergence of resistant cancer cell clones only in the presence of IFN-γ within the tumour microenvironment. Moreover, we show that exposure of tumours to IFN-γ-producing antigen-specific CTLs in vivo results in copy-number alterations (CNAs) associated with DNA damage response and modulation of DNA editing/repair gene expression. These results suggest that enhanced genetic instability might be one of the mechanisms by which CTLs and IFN-γ immunoedits tumours, altering their immune resistance as a result of genetic evolution.
dc.languageEnglish
dc.publisherNATURE PUBLISHING GROUP
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleIFN-gamma is required for cytotoxic T cell-dependent cancer genome immunoediting
dc.typeJournal Article
dc.identifier.doi10.1038/ncomms14607
melbourne.affiliation.departmentSir Peter MacCallum Department of Oncology
melbourne.source.titleNature Communications
melbourne.source.volume8
melbourne.source.issue1
dc.rights.licenseCC BY
melbourne.elementsid1190850
melbourne.contributor.authorThomas, David
dc.identifier.eissn2041-1723
melbourne.accessrightsOpen Access


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