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PDL1 signals through conserved sequence motifs to overcome interferon-mediated cytotoxicity
dc.creator | Gato Cañas, María | es_ES |
dc.creator | Zuazo Ibarra, Miren | es_ES |
dc.creator | Arasanz Esteban, Hugo | es_ES |
dc.creator | Ibáñez-Vea, María | es_ES |
dc.creator | Lorenzo, Laura | es_ES |
dc.creator | Fernandez-Hinojal, Gonzalo | es_ES |
dc.creator | Vera García, Ruth | es_ES |
dc.creator | Smerdou, Cristian | es_ES |
dc.creator | Martisova, Eva | es_ES |
dc.creator | Arozarena Martinicorena, Imanol | es_ES |
dc.creator | Wellbrock, Claudia | es_ES |
dc.creator | Llopiz, Diana | es_ES |
dc.creator | Ruiz, Marta | es_ES |
dc.creator | Sarobe, Pablo | es_ES |
dc.creator | Breckpot, Karine | es_ES |
dc.creator | Kochan, Grazyna | es_ES |
dc.creator | Escors Murugarren, David | es_ES |
dc.date.accessioned | 2022-08-08T11:47:33Z | |
dc.date.available | 2022-08-08T11:47:33Z | |
dc.date.issued | 2017 | |
dc.identifier.citation | Gato-Cañas, M.; Ibañez-Vea, M.; Zuazo, M.; Arasanz, H.; Lorenzo, L.; Fernandez-Hinojal, G.; Vera, R.; Smerdou, C.; Martisova, E.; Arozarena, I.; Wellbrock, C.; Llopiz, D.; Ruiz, M.; Sarobe, P.; Breckpot, K.; Kochan, G.; Escors, D.. (2017). PDL1 signals through conserved sequence motifs to overcome interferon-mediated cytotoxicity. Cell Reports. 20,8, pp. 1818-1829 | en |
dc.identifier.issn | 2211-1247 | |
dc.identifier.uri | https://hdl.handle.net/2454/43728 | |
dc.description.abstract | PDL1 blockade produces remarkable clinical responses, thought to occur by T cell reactivation through prevention of PDL1-PD1 T cell inhibitory interactions. Here, we find that PDL1 cell-intrinsic signaling protects cancer cells from interferon (IFN) cytotoxicity and accelerates tumor progression. PDL1 inhibited IFN signal transduction through a conserved class of sequence motifs that mediate crosstalk with IFN signaling. Abrogation of PDL1 expression or antibody-mediated PDL1 blockade strongly sensitized cancer cells to IFN cytotoxicity through a STAT3/caspase-7-dependent pathway. Moreover, somatic mutations found in human carcinomas within these PDL1 sequence motifs disrupted motif regulation, resulting in PDL1 molecules with enhanced protective activities from type I and type II IFN cytotoxicity. Overall, our results reveal a mode of action of PDL1 in cancer cells as a first line of defense against IFN cytotoxicity. | en |
dc.description.sponsorship | This project was funded by a crowdfunding project by FECYT (PRECIPITA, Spain), an FIS grant (PI14/00579) from the Instituto de Salud Carlos III, a grant from the Government of Navarre (Spain; BMED 033-2014), and a grant from Fundación Caixa (Spain) to G.K. We thank the SARAY Foundation (Navarra, Spain) and Sandra Ibarra’s foundation for financial support. M.G. is funded by a PhD fellowship granted by the Government of Navarre. M.Z. is funded by a fellowship granted by Universidad Pública de Navarra (UPNA), Spain. M.I.V. is funded by a Sara Borrel Fellowship. I.A. is funded by a Miguel Servet Fellowship. K.B. received funding from Kom Op Tegen Kanker (Belgium). We especially thank Luciano Escors, Lucia Murugarren, and family for their donations and overall support, as well as all the donors who contributed to the ‘PRECIPITA’ project. D.E. is funded by a Miguel Servet Fellowship (CP12/03114) awarded by the Instituto de Salud Carlos III (Spain). | en |
dc.format.mimetype | application/pdf | en |
dc.language.iso | eng | en |
dc.publisher | Elsevier | en |
dc.relation.ispartof | Cell Reports, 2017, 20 (8), pp. 1818-1829 | en |
dc.rights | © 2017 The Authors. This is an open access article under the CC BY-NC-ND license | en |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.subject | PDL1 | en |
dc.subject | PD-L1 | en |
dc.subject | B7-H1 | en |
dc.subject | CD274 | en |
dc.subject | PD1 | en |
dc.subject | Interferon | en |
dc.subject | Signal transduction | en |
dc.subject | Immunotherapy | en |
dc.title | PDL1 signals through conserved sequence motifs to overcome interferon-mediated cytotoxicity | en |
dc.type | Artículo / Artikulua | es |
dc.type | info:eu-repo/semantics/article | en |
dc.date.updated | 2022-08-08T11:05:19Z | |
dc.contributor.department | Ciencias de la Salud | es_ES |
dc.contributor.department | Osasun Zientziak | eu |
dc.rights.accessRights | Acceso abierto / Sarbide irekia | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | en |
dc.identifier.doi | 10.1016/j.celrep.2017.07.075 | |
dc.relation.publisherversion | https://doi.org/10.1016/j.celrep.2017.07.075 | |
dc.type.version | Versión publicada / Argitaratu den bertsioa | es |
dc.type.version | info:eu-repo/semantics/publishedVersion | en |
dc.contributor.funder | Universidad Pública de Navarra / Nafarroako Unibertsitate Publikoa | es |
dc.contributor.funder | Gobierno de Navarra / Nafarroako Gobernua | es |