dc.contributor.author | Waaler, Jo | |
dc.contributor.author | Mygland, Line | |
dc.contributor.author | Tveita, Anders Aune | |
dc.contributor.author | Strand, Martin Frank | |
dc.contributor.author | Solberg, Nina | |
dc.contributor.author | Olsen, Petter Angell | |
dc.contributor.author | Aizenshtadt, Aleksandra | |
dc.contributor.author | Fauskanger, Marte | |
dc.contributor.author | Lund, Kaja | |
dc.contributor.author | Brinch, Shoshy Alam | |
dc.contributor.author | Lycke, Max | |
dc.contributor.author | Dybing, Elisabeth | |
dc.contributor.author | Nygaard, Vegard | |
dc.contributor.author | Bøe, Sigurd | |
dc.contributor.author | Heintz, Karen Marie | |
dc.contributor.author | Hovig, Eivind | |
dc.contributor.author | Hammarström, Clara Louise | |
dc.contributor.author | Corthay, Alexandre | |
dc.contributor.author | Krauss, Stefan | |
dc.date.accessioned | 2021-12-10T08:42:33Z | |
dc.date.available | 2021-12-10T08:42:33Z | |
dc.date.created | 2020-05-08T10:22:59Z | |
dc.date.issued | 2020 | |
dc.identifier.citation | Communications Biology. 2020, 3, 1-13. | en_US |
dc.identifier.issn | 2399-3642 | |
dc.identifier.uri | https://hdl.handle.net/11250/2833692 | |
dc.description.abstract | The development of immune checkpoint inhibitors represents a major breakthrough in cancer therapy. Nevertheless, a substantial number of patients fail to respond to checkpoint pathway blockade. Evidence for WNT/β-catenin signaling-mediated immune evasion is found in a subset of cancers including melanoma. Currently, there are no therapeutic strategies available for targeting WNT/β-catenin signaling. Here we show that a specific small-molecule tankyrase inhibitor, G007-LK, decreases WNT/β-catenin and YAP signaling in the syngeneic murine B16-F10 and Clone M-3 melanoma models and sensitizes the tumors to anti-PD-1 immune checkpoint therapy. Mechanistically, we demonstrate that the synergistic effect of tankyrase and checkpoint inhibitor treatment is dependent on loss of β-catenin in the tumor cells, anti-PD-1-stimulated infiltration of T cells into the tumor and induction of an IFNγ- and CD8+ T cell-mediated anti-tumor immune response. Our study uncovers a combinatorial therapeutical strategy using tankyrase inhibition to overcome β-catenin-mediated resistance to immune checkpoint blockade in melanoma. | en_US |
dc.language.iso | eng | en_US |
dc.rights | Navngivelse 4.0 Internasjonal | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/deed.no | * |
dc.title | Tankyrase inhibition sensitizes melanoma to PD-1 immune checkpoint blockade in syngeneic mouse models | en_US |
dc.type | Peer reviewed | en_US |
dc.type | Journal article | en_US |
dc.description.version | publishedVersion | en_US |
dc.source.pagenumber | 1-13 | en_US |
dc.source.volume | 3 | en_US |
dc.source.journal | Communications Biology | en_US |
dc.identifier.doi | 10.1038/s42003-020-0916-2 | |
dc.identifier.cristin | 1809908 | |
dc.relation.project | Norges forskningsråd: 287990 | en_US |
dc.relation.project | Norges forskningsråd: 262613 | en_US |
dc.relation.project | Norges forskningsråd: 267639 | en_US |
dc.relation.project | Norges forskningsråd: 262814 | en_US |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |