ReviewFrontiers in immunology2018
CD137 (4-1BB) Signalosome: Complexity Is a Matter of TRAFs.
Review in Frontiers in immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
79 citing papers in PubMed, 123 citations in OpenAlex.
- FTL008.16, a 5T4-Conditional 4-1BB bispecific antibody, potently enhances antitumor immunity via tumor-directed t-cell activation.Oncoimmunology · 2026Article
- Structural dynamics and pH-regulated membrane binding of the TRAF2-NC trimer.Protein science : a publication of the Protein Society · 2026Article
- CD137 agonists in mice suppress germinal center responses by increasing the immunosuppressive activity of follicular regulatory T-cells.The EMBO journal · 2026Article
- Fas acts as a T cell co-stimulatory receptor via both death domain-independent and -dependent mechanisms.Cell death and differentiation · 2026Article
- Single-cell profiling of HDAC inhibitor-induced EBV lytic heterogeneity defines abortive and refractory states in B lymphoblasts.PLoS pathogens · 2026Article
- De novo protein design: a transformative frontier in clinical protein applications.Journal of translational medicine · 2026Review
- CAR Intrinsic Design Pre-Shapes Transcriptional and Metabolic Networks in CAR T Cells.Metabolites · 2026Article
- Development of a nanoparticle-based immunotherapy targeting CD137 for nasopharyngeal carcinoma treatment.Theranostics · 2026Article
- CD28 signaling complexes are correlated with patient outcomes in anti-CD19 41BB-costimulation CAR T cell therapy.Journal for immunotherapy of cancer · 2025Article
- CD137L promotes immune surveillance in melanoma via HLTF regulation.Nature communications · 2025Article
- 4-1BB stimulation with concomitant inactivation of adenosine A2B receptors enhances CD8+ T cell antitumor response.The Journal of clinical investigation · 2025Article
- MD Simulation Reveals a Trimerization-Enhanced Interaction of CD137L with CD137.International journal of molecular sciences · 2025Article
- CD137-expressing regulatory T cells in cancer and autoimmune diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- The role of immune checkpoint molecules in cancers.Frontiers in immunology · 2025Review
- SLAMF7 (CD319) enhances cytotoxic T-cell differentiation and sensitizes CD8Frontiers in immunology · 2025Article
- Generating tumor-specific T cells based on a head and neck cancer organoid for adoptive cell therapy.Frontiers in immunology · 2025Article
- Target-conditioned diffusion generates potent TNFR superfamily antagonists and agonists.Science (New York, N.Y.) · 2024Article
- Tumor Microenvironment Drives the Cross-Talk Between Co-Stimulatory and Inhibitory Molecules in Tumor-Infiltrating Lymphocytes: Implications for Optimizing Immunotherapy Outcomes.International journal of molecular sciences · 2024Review
- Extracellular vesicle surface display enhances the therapeutic efficacy and safety profile of cancer immunotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Human/mouse CD137 agonist, JNU-0921, effectively shrinks tumors through enhancing the cytotoxicity of CD8Science advances · 2024Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CD137 (4-1BB, Tnsfr9) is a member of the TNF-receptor (TNFR) superfamily without known intrinsic enzymatic activity in its cytoplasmic domain. Hence, akin to other members of the TNFR family, it relies on the TNFR-Associated-Factor (TRAF) family of adaptor proteins to build the CD137 signalosome for transducing signals into the cell. Thus, upon CD137 activation by binding of CD137L trimers or by crosslinking with agonist monoclonal antibodies, TRAF1, TRAF2, and TRAF3 are readily recruited to the cytoplasmic domain of CD137, likely as homo- and/or heterotrimers with different configurations, initiating the construction of the CD137 signalosome. The formation of TRAF2-RING dimers between TRAF2 molecules from contiguous trimers would help to establish a multimeric structure of TRAF-trimers that is probably essential for CD137 signaling. In addition, available studies have identified a large number of proteins that are recruited to CD137:TRAF complexes including ubiquitin ligases and proteases, kinases, and modulatory proteins. Working in a coordinated fashion, these CD137-signalosomes will ultimately promote CD137-mediated T cell proliferation and survival and will endow T cells with stronger effector functions. Current evidence allows to envision the molecular events that might take place in the early stages of CD137-signalosome formation, underscoring the key roles of TRAFs and of K63 and K48-ubiquitination of target proteins in the signaling process. Understanding the composition and fine regulation of CD137-signalosomes assembly and disassembly will be key to improve the therapeutic activities of chimeric antigen receptors (CARs) encompassing the CD137 cytoplasmic domain and a new generation of CD137 agonists for the treatment of cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.