Search: id:"swepub:oai:lup.lub.lu.se:ca6e18f0-8052-489a-b7cc-7c04728ddb19" >
CD137 (4-1BB) costi...
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Otano, ItziarSpanish Center for Biomedical Research Network in Oncology (CIBERONC),12 de Octubre University Hospital,Spanish National Cancer Research Center (CNIO),University of Navarra
(author)
CD137 (4-1BB) costimulation of CD8+ T cells is more potent when provided in cis than in trans with respect to CD3-TCR stimulation
- Article/chapterEnglish2021
Publisher, publication year, extent ...
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2021-12-15
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Springer Science and Business Media LLC,2021
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LIBRIS-ID:oai:lup.lub.lu.se:ca6e18f0-8052-489a-b7cc-7c04728ddb19
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https://lup.lub.lu.se/record/ca6e18f0-8052-489a-b7cc-7c04728ddb19URI
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https://doi.org/10.1038/s41467-021-27613-wDOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:art swepub-publicationtype
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Subject category:ref swepub-contenttype
Notes
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CD137 (4-1BB; TNFSR9) is an activation-induced surface receptor that through costimulation effects provide antigen-primed T cells with augmented survival, proliferation and effector functions as well as metabolic advantages. These immunobiological mechanisms are being utilised for cancer immunotherapy with agonist CD137-binding and crosslinking-inducing agents that elicit CD137 intracellular signaling. In this study, side-by-side comparisons show that provision of CD137 costimulation in-cis with regard to the TCR-CD3-ligating cell is superior to that provided in-trans in terms of T cell activation, proliferation, survival, cytokine secretion and mitochondrial fitness in mouse and human. Cis ligation of CD137 relative to the TCR-CD3 complex results in more intense canonical and non-canonical NF-κB signaling and provides a more robust induction of cell cycle and DNA damage repair gene expression programs. Here we report that the superiority of cis versus trans CD137-costimulation is readily observed in vivo and is relevant for understanding the immunotherapeutic effects of CAR T cells and CD137 agonistic therapies currently undergoing clinical trials, which may provide costimulation either in cis or in trans.
Subject headings and genre
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Azpilikueta, ArantzaSpanish Center for Biomedical Research Network in Oncology (CIBERONC),University of Navarra,Health Research Institute of Navarra (IDISNA)
(author)
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Glez-Vaz, JavierUniversity of Navarra,Health Research Institute of Navarra (IDISNA),Spanish Center for Biomedical Research Network in Oncology (CIBERONC)
(author)
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Alvarez, MaiteHealth Research Institute of Navarra (IDISNA),University of Navarra,Spanish Center for Biomedical Research Network in Oncology (CIBERONC)
(author)
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Medina-Echeverz, JoséBavarian Nordic GmbH
(author)
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Cortés-Domínguez, IvanHealth Research Institute of Navarra (IDISNA),University of Navarra
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Ortiz-de-Solorzano, CarlosSpanish Center for Biomedical Research Network in Oncology (CIBERONC),University of Navarra,Health Research Institute of Navarra (IDISNA)
(author)
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Ellmark, PeterLund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH,Alligator Biosciences AB(Swepub:lu)immt-pel
(author)
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Fritzell, SaraAlligator Biosciences AB(Swepub:lu)med-sfz
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Hernandez-Hoyos, GabrielaAptevo Therapeutics
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Nelson, Michelle HaseAptevo Therapeutics
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Ochoa, María CarmenUniversity Clinic of Navarra,Spanish Center for Biomedical Research Network in Oncology (CIBERONC),Health Research Institute of Navarra (IDISNA),University of Navarra
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Bolaños, ElixabetSpanish Center for Biomedical Research Network in Oncology (CIBERONC),University Clinic of Navarra,Health Research Institute of Navarra (IDISNA)
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Cuculescu, DoinaSpanish Center for Biomedical Research Network in Oncology (CIBERONC),Health Research Institute of Navarra (IDISNA),University of Navarra
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Jaúregui, PatriciaHealth Research Institute of Navarra (IDISNA),Spanish Center for Biomedical Research Network in Oncology (CIBERONC)
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Sanchez-Gregorio, SandraHealth Research Institute of Navarra (IDISNA),University of Navarra,University Clinic of Navarra,Spanish Center for Biomedical Research Network in Oncology (CIBERONC)
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Etxeberria, IñakiHealth Research Institute of Navarra (IDISNA),University of Navarra,Spanish Center for Biomedical Research Network in Oncology (CIBERONC)
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Rodriguez-Ruiz, María E.Spanish Center for Biomedical Research Network in Oncology (CIBERONC),Health Research Institute of Navarra (IDISNA),University of Navarra,University Clinic of Navarra
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Sanmamed, Miguel F.Spanish Center for Biomedical Research Network in Oncology (CIBERONC),University Clinic of Navarra,Health Research Institute of Navarra (IDISNA),University of Navarra
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Teijeira, ÁlvaroUniversity of Navarra,Health Research Institute of Navarra (IDISNA),University Clinic of Navarra,Spanish Center for Biomedical Research Network in Oncology (CIBERONC)
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Berraondo, PedroSpanish Center for Biomedical Research Network in Oncology (CIBERONC),University of Navarra,Health Research Institute of Navarra (IDISNA)
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Melero, IgnacioHealth Research Institute of Navarra (IDISNA),University of Navarra,Spanish National Cancer Research Center (CNIO),University Clinic of Navarra,12 de Octubre University Hospital,Spanish Center for Biomedical Research Network in Oncology (CIBERONC)
(author)
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Spanish Center for Biomedical Research Network in Oncology (CIBERONC)12 de Octubre University Hospital
(creator_code:org_t)
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In:Nature Communications: Springer Science and Business Media LLC12:12041-1723
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Otano, Itziar
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Azpilikueta, Ara ...
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Glez-Vaz, Javier
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Alvarez, Maite
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Medina-Echeverz, ...
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Cortés-Domínguez ...
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Ortiz-de-Solorza ...
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Ellmark, Peter
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Fritzell, Sara
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Ochoa, María Car ...
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Bolaños, Elixabe ...
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Cuculescu, Doina
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Jaúregui, Patric ...
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Sanchez-Gregorio ...
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Etxeberria, Iñak ...
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Sanmamed, Miguel ...
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Teijeira, Álvaro
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