CD137 (4-1BB) requires physically associated cIAPs for signal transduction and antitumor effects Article Swipe
Javier Glez‐Vaz
,
Arantza Azpilikueta
,
María C. Ochoa
,
Irene Olivera
,
Gabriel Gomis
,
Asunta Cirella
,
Carlos Luri‐Rey
,
Maite Álvarez
,
José Luis Perez‐Gracia
,
Sergio Ciordia
,
Iñaki Eguren‐Santamaría
,
Raluca Alexandru
,
Pedro Berraondo
,
Carlos de Andrea
,
Álvaro Teijeira
,
Fernando J. Corrales
,
Juan M. Zapata
,
Ignacio Melero
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1126/sciadv.adf6692
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1126/sciadv.adf6692
CD137 (4-1BB) is a member of the TNFR family that mediates potent T cell costimulatory signals upon ligation by CD137L or agonist monoclonal antibodies (mAbs). CD137 agonists attain immunotherapeutic antitumor effects in cancer mouse models, and multiple agents of this kind are undergoing clinical trials. We show that cIAP1 and cIAP2 are physically associated with the CD137 signaling complex. Moreover, cIAPs are required for CD137 signaling toward the NF-κB and MAPK pathways and for costimulation of human and mouse T lymphocytes. Functional evidence was substantiated with SMAC mimetics that trigger cIAP degradation and by transfecting cIAP dominant-negative variants. Antitumor effects of agonist anti-CD137 mAbs are critically dependent on the integrity of cIAPs in cancer mouse models, and cIAPs are also required for signaling from CARs encompassing CD137’s cytoplasmic tail.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1126/sciadv.adf6692
- https://www.science.org/doi/pdf/10.1126/sciadv.adf6692?download=true
- OA Status
- gold
- Cited By
- 9
- References
- 84
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4385971203
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4385971203Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1126/sciadv.adf6692Digital Object Identifier
- Title
-
CD137 (4-1BB) requires physically associated cIAPs for signal transduction and antitumor effectsWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-08-18Full publication date if available
- Authors
-
Javier Glez‐Vaz, Arantza Azpilikueta, María C. Ochoa, Irene Olivera, Gabriel Gomis, Asunta Cirella, Carlos Luri‐Rey, Maite Álvarez, José Luis Perez‐Gracia, Sergio Ciordia, Iñaki Eguren‐Santamaría, Raluca Alexandru, Pedro Berraondo, Carlos de Andrea, Álvaro Teijeira, Fernando J. Corrales, Juan M. Zapata, Ignacio MeleroList of authors in order
- Landing page
-
https://doi.org/10.1126/sciadv.adf6692Publisher landing page
- PDF URL
-
https://www.science.org/doi/pdf/10.1126/sciadv.adf6692?download=trueDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.science.org/doi/pdf/10.1126/sciadv.adf6692?download=trueDirect OA link when available
- Concepts
-
CD137, Signal transduction, Agonist, Monoclonal antibody, Cancer research, Immunology, Chemistry, Cell biology, Biology, Antibody, Receptor, BiochemistryTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
9Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 3, 2024: 5, 2023: 1Per-year citation counts (last 5 years)
- References (count)
-
84Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.upon | 16 |
| abstract_inverted_index.with | 54, 85 |
| abstract_inverted_index.CD137 | 0, 25, 56, 64 |
| abstract_inverted_index.cIAP1 | 48 |
| abstract_inverted_index.cIAP2 | 50 |
| abstract_inverted_index.cIAPs | 60, 111, 117 |
| abstract_inverted_index.human | 76 |
| abstract_inverted_index.mouse | 33, 78, 114 |
| abstract_inverted_index.tail. | 128 |
| abstract_inverted_index.CD137L | 19 |
| abstract_inverted_index.NF-κB | 68 |
| abstract_inverted_index.agents | 37 |
| abstract_inverted_index.attain | 27 |
| abstract_inverted_index.cancer | 32, 113 |
| abstract_inverted_index.family | 8 |
| abstract_inverted_index.member | 4 |
| abstract_inverted_index.potent | 11 |
| abstract_inverted_index.toward | 66 |
| abstract_inverted_index.(4-1BB) | 1 |
| abstract_inverted_index.(mAbs). | 24 |
| abstract_inverted_index.agonist | 21, 101 |
| abstract_inverted_index.effects | 30, 99 |
| abstract_inverted_index.models, | 34, 115 |
| abstract_inverted_index.signals | 15 |
| abstract_inverted_index.trials. | 44 |
| abstract_inverted_index.trigger | 89 |
| abstract_inverted_index.agonists | 26 |
| abstract_inverted_index.clinical | 43 |
| abstract_inverted_index.complex. | 58 |
| abstract_inverted_index.evidence | 82 |
| abstract_inverted_index.ligation | 17 |
| abstract_inverted_index.mediates | 10 |
| abstract_inverted_index.mimetics | 87 |
| abstract_inverted_index.multiple | 36 |
| abstract_inverted_index.pathways | 71 |
| abstract_inverted_index.required | 62, 120 |
| abstract_inverted_index.Antitumor | 98 |
| abstract_inverted_index.CD137’s | 126 |
| abstract_inverted_index.Moreover, | 59 |
| abstract_inverted_index.antitumor | 29 |
| abstract_inverted_index.dependent | 106 |
| abstract_inverted_index.integrity | 109 |
| abstract_inverted_index.signaling | 57, 65, 122 |
| abstract_inverted_index.variants. | 97 |
| abstract_inverted_index.Functional | 81 |
| abstract_inverted_index.anti-CD137 | 102 |
| abstract_inverted_index.antibodies | 23 |
| abstract_inverted_index.associated | 53 |
| abstract_inverted_index.critically | 105 |
| abstract_inverted_index.monoclonal | 22 |
| abstract_inverted_index.physically | 52 |
| abstract_inverted_index.undergoing | 42 |
| abstract_inverted_index.cytoplasmic | 127 |
| abstract_inverted_index.degradation | 91 |
| abstract_inverted_index.encompassing | 125 |
| abstract_inverted_index.lymphocytes. | 80 |
| abstract_inverted_index.transfecting | 94 |
| abstract_inverted_index.costimulation | 74 |
| abstract_inverted_index.costimulatory | 14 |
| abstract_inverted_index.substantiated | 84 |
| abstract_inverted_index.dominant-negative | 96 |
| abstract_inverted_index.immunotherapeutic | 28 |
| cited_by_percentile_year.max | 98 |
| cited_by_percentile_year.min | 89 |
| corresponding_author_ids | https://openalex.org/A5029243551, https://openalex.org/A5058524912 |
| countries_distinct_count | 2 |
| institutions_distinct_count | 18 |
| corresponding_institution_ids | https://openalex.org/I40120149, https://openalex.org/I4210091816, https://openalex.org/I4210103477, https://openalex.org/I4210112085, https://openalex.org/I4210135003, https://openalex.org/I4210158561, https://openalex.org/I63634437, https://openalex.org/I88155538 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.8299999833106995 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.8548982 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |