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CD137 (4-1BB) costi...
CD137 (4-1BB) costimulation of CD8+ T cells is more potent when provided in cis than in trans with respect to CD3-TCR stimulation
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- Otano, Itziar (författare)
- Spanish National Cancer Research Center (CNIO),University of Navarra,12 de Octubre University Hospital,Spanish Center for Biomedical Research Network in Oncology (CIBERONC)
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- Azpilikueta, Arantza (författare)
- Health Research Institute of Navarra (IDISNA),Spanish Center for Biomedical Research Network in Oncology (CIBERONC),University of Navarra
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- Glez-Vaz, Javier (författare)
- University of Navarra,Spanish Center for Biomedical Research Network in Oncology (CIBERONC),Health Research Institute of Navarra (IDISNA)
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- Alvarez, Maite (författare)
- Health Research Institute of Navarra (IDISNA),Spanish Center for Biomedical Research Network in Oncology (CIBERONC),University of Navarra
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- Medina-Echeverz, José (författare)
- Bavarian Nordic GmbH
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- Cortés-Domínguez, Ivan (författare)
- Health Research Institute of Navarra (IDISNA),University of Navarra
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- Ortiz-de-Solorzano, Carlos (författare)
- Spanish Center for Biomedical Research Network in Oncology (CIBERONC),University of Navarra,Health Research Institute of Navarra (IDISNA)
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- Ellmark, Peter (författare)
- Lund 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
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- Fritzell, Sara (författare)
- Alligator Biosciences AB
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- Hernandez-Hoyos, Gabriela (författare)
- Aptevo Therapeutics
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- Nelson, Michelle Hase (författare)
- Aptevo Therapeutics
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- Ochoa, María Carmen (författare)
- Spanish Center for Biomedical Research Network in Oncology (CIBERONC),University of Navarra,Health Research Institute of Navarra (IDISNA),University Clinic of Navarra
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- Bolaños, Elixabet (författare)
- Spanish Center for Biomedical Research Network in Oncology (CIBERONC),University Clinic of Navarra,Health Research Institute of Navarra (IDISNA)
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- Cuculescu, Doina (författare)
- University of Navarra,Spanish Center for Biomedical Research Network in Oncology (CIBERONC),Health Research Institute of Navarra (IDISNA)
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- Jaúregui, Patricia (författare)
- Spanish Center for Biomedical Research Network in Oncology (CIBERONC),Health Research Institute of Navarra (IDISNA)
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- Sanchez-Gregorio, Sandra (författare)
- University of Navarra,Spanish Center for Biomedical Research Network in Oncology (CIBERONC),Health Research Institute of Navarra (IDISNA),University Clinic of Navarra
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- Etxeberria, Iñaki (författare)
- University of Navarra,Spanish Center for Biomedical Research Network in Oncology (CIBERONC),Health Research Institute of Navarra (IDISNA)
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- Rodriguez-Ruiz, María E. (författare)
- University of Navarra,University Clinic of Navarra,Spanish Center for Biomedical Research Network in Oncology (CIBERONC),Health Research Institute of Navarra (IDISNA)
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- Sanmamed, Miguel F. (författare)
- University of Navarra,University Clinic of Navarra,Spanish Center for Biomedical Research Network in Oncology (CIBERONC),Health Research Institute of Navarra (IDISNA)
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- Teijeira, Álvaro (författare)
- University of Navarra,University Clinic of Navarra,Health Research Institute of Navarra (IDISNA),Spanish Center for Biomedical Research Network in Oncology (CIBERONC)
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- Berraondo, Pedro (författare)
- University of Navarra,Health Research Institute of Navarra (IDISNA),Spanish Center for Biomedical Research Network in Oncology (CIBERONC)
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- Melero, Ignacio (författare)
- 12 de Octubre University Hospital,Spanish National Cancer Research Center (CNIO),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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(creator_code:org_t)
- 2021-12-15
- 2021
- Engelska.
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://www.nature.c...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
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- art (ämneskategori)
- ref (ämneskategori)
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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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Hernandez-Hoyos, ...
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Nelson, Michelle ...
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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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Rodriguez-Ruiz, ...
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Sanmamed, Miguel ...
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Teijeira, Álvaro
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Berraondo, Pedro
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Melero, Ignacio
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