ArticleCancer immunology, immunotherapy : CII2011
Signals through 4-1BB inhibit T regulatory cells by blocking IL-9 production enhancing antitumor responses.
Article in Cancer immunology, immunotherapy : CII, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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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
42 citing papers in PubMed, 71 citations in OpenAlex.
- IgG2a-formatted 4-1BB agonism combined with S100A9 inhibition enhances T cell activation and tumor control in a preclinical model of multiple myeloma.Journal of experimental & clinical cancer research : CR · 2026Article
- Macrophage-intrinsic and IL-9-dependent arginine metabolism promotes lung tumor growth.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Regulatory T cell and endothelial cell crosstalk.Nature reviews. Immunology · 2025Review
- PET-based immunomapping of intratumoral CD4Science advances · 2025Article
- CD137-expressing regulatory T cells in cancer and autoimmune diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Comprehensive multi-omics analysis reveals the prognostic and immune regulatory characteristics of the PTPN family in osteosarcoma.PloS one · 2025Article
- The World according to IL-9.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- The Dichotomy of Interleukin-9 Function in the Tumor Microenvironment.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2023Review
- Nasopharyngeal carcinoma cells promote regulatory T cell development and suppressive activity via CD70-CD27 interaction.Nature communications · 2023Article
- Article
- NF-κB in control of regulatory T cell development, identity, and function.Journal of molecular medicine (Berlin, Germany) · 2022Review
- IL-1β promotes IL-9-producing Th cell differentiation in IL-2-limiting conditions through the inhibition of BCL6.Frontiers in immunology · 2022Article
- The Road Less Taken: Less Appreciated Pathways for Manipulating CD8Frontiers in immunology · 2022Review
- CD137Cancers · 2021Review
- Immune-Checkpoint Inhibitors in B-Cell Lymphoma.Cancers · 2021Review
- Crosstalk between the Producers and Immune Targets of IL-9.Immune network · 2020Review
- Article
- The Murine CD137/CD137 Ligand Signalosome: A Signal Platform Generating Signal Complexity.Frontiers in immunology · 2020Review
- CD137 agonist induces gastric cancer cell apoptosis by enhancing the functions of CD8Cancer cell international · 2020Article
- A mathematical model of combined CD8 T cell costimulation by 4-1BB (CD137) and OX40 (CD134) receptors.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Previous studies from our laboratory indicate that intratumoral (i.t.) injections of CpG-ODN are the most effective adjuvant strategy to induce an antitumor immune response in tolerant BALB-neuT mice but insufficient for tumor eradication. We evaluated whether this treatment strategy could be enhanced by the presence of anti-OX40 and anti-4-1BB antibodies. Treatment with anti-4-1BB resulted in a greater antitumor response than anti-OX40. The results indicate that anti-4-1BB but not anti-OX40 inhibited the suppressive function of T regulatory cells (Tregs). Through microarray analysis we evaluated the mechanism by which anti-4-1BB inhibits iTregs using the Foxp3-GFP mice. We observed specific transcriptional differences in over 100 genes in iTregs treated with anti-4-1BB, and selected those genes that remained unaffected by exposure to anti-OX40. Interleukin 9 was transcriptionally down-regulated 28-fold by anti-4-1BB treatment, and this was matched by a significant reduction of IL-9 secretion by iTregs. Furthermore, blockade of the common γ-chain receptor resulted in the inhibition of iTreg-suppressive function. More importantly, neutralization of IL-9 plus i.t. injections of CpG-ODN induces tumor rejection in BALB-neuT and MUC-1 tolerant transgenic mice. These results indicate that IL-9 plays a role in iTreg biology during the tumor inflammatory process enhancing/promoting the suppressive function of these cells and that the blockade of IL-9 could serve as a novel strategy to modulate the function of Tregs to enhance the antitumor effect of tumor vaccines.
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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.