ArticleNature communications2021
CD137 (4-1BB) costimulation of CD8
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 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.
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Who cites it
51 citing papers in PubMed, 86 citations in OpenAlex.
- Tumor-infiltrated double-negative regulatory T cells predict outcome of T cell-based immunotherapy in nasopharyngeal carcinoma.Cell reports. Medicine · 2025Trial
- Immunophenotyping of Cellular Therapy Products Against Oncogenic and Viral Targets.Methods in molecular biology (Clifton, N.J.) · 2027Article
- FTL008.16, a 5T4-Conditional 4-1BB bispecific antibody, potently enhances antitumor immunity via tumor-directed t-cell activation.Oncoimmunology · 2026Article
- CD137 agonists in mice suppress germinal center responses by increasing the immunosuppressive activity of follicular regulatory T-cells.The EMBO journal · 2026Article
- Molecular Engineering of Aptamers for Glioblastoma Therapy: From Simple Antagonists to AI-Driven Approaches, a Narrative Review.International journal of molecular sciences · 2026Review
- 4-1BB Expression and Signaling Regulates MAIT Cell Activation and Effector Functions.Immunology and cell biology · 2026Article
- Igniting cold tumors: reprogramming the tumor immune microenvironment with dual-payload ADCs in combination with PD-L1&4-1BB bispecific antibodies.Journal for immunotherapy of cancer · 2026Article
- A Comprehensive Literature Review and Case Report of Severe Lymphoproliferative Disease Secondary toJournal of clinical medicine · 2026Article
- Spatial and Single-Cell Transcriptomics Reveal Keratinocytes as Key Players in Vulvar Lichen Sclerosus Pathogenesis.The Journal of investigative dermatology · 2026Article
- Dextran-based T-cell expansion nanoparticles for manufacturing CAR T cells with augmented efficacy.Nature communications · 2026Article
- Neuroimmune Mechanisms in Traumatic Brain Injury and Cancer: Parallel Courses or Existence in Different Orbits.Biomedicines · 2026Review
- The tumor microenvironment as a key regulator of radiotherapy response.Frontiers in immunology · 2026Review
- Cis- and trans-binding chimeric costimulatory receptors enhance T-cell fitness and tumor control.Cellular & molecular immunology · 2026Article
- In situ DC-primed vaccine combined with CD137 agonist elicits long-lasting antitumor immunity through cDC1-mediated tumor antigen-specific CD8Journal for immunotherapy of cancer · 2025Article
- Enhancement of CAR-T cell efficacy and persistence via CD30 costimulation and NF-κB signaling.Molecular cancer · 2025Article
- CEA-4-1BBL: CEACAM5-Targeted 4-1BB Ligand Fusion Proteins for Cis Co-Stimulation with CEA-TCB.Antibodies (Basel, Switzerland) · 2025Article
- Primary Sequence-Intrinsic Immune Evasion by Viral Proteins Guides CTL-Based Vaccine Strategies.Viruses · 2025Review
- Serotonin receptor 5-HTJournal for immunotherapy of cancer · 2025Article
- One-carbon metabolism is distinct metabolic signature for proliferative intermediate exhausted T cells of ICB-resistant cancer patients.Cell death discovery · 2025Article
- Current Trends in Clinical Trials of Prodrugs.Pharmaceuticals (Basel, Switzerland) · 2025Review
Corrections and comments
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Authors and funding
22 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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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.