ArticleBlood2015
Direct and immune-mediated cytotoxicity of interleukin-21 contributes to antitumor effects in mantle cell lymphoma.
Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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.
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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
20 citing papers in PubMed, 34 citations in OpenAlex.
- Exploring the prognostic value of T follicular helper cell levels in chronic lymphocytic leukemia.Scientific reports · 2024Article
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- Engineered murine IL-21-secreting leukemia cells induce granzyme BCancer immunology, immunotherapy : CII · 2023Article
- Implications of IL-21 in solid tumor therapy.Medical oncology (Northwood, London, England) · 2023Review
- Roles of PI3Kγ and PI3Kδ in mantle cell lymphoma proliferation and migration contributing to efficacy of the PI3Kγ/δ inhibitor duvelisib.Scientific reports · 2023Article
- The application of Interleukin-2 family cytokines in tumor immunotherapy research.Frontiers in immunology · 2023Review
- Potential Anti-Tumor Activity of Nardoguaianone L Isolated fromMolecules (Basel, Switzerland) · 2022Article
- Mantle cell lymphoma polarizes tumor-associated macrophages into M2-like macrophages, which in turn promote tumorigenesis.Blood advances · 2021Article
- The Assessment of IL-21 and IL-22 at the mRNA Level in Tumor Tissue and Protein Concentration in Serum and Peritoneal Fluid in Patients with Ovarian Cancer.Journal of clinical medicine · 2021Article
- Article
- Cystatin-B Negatively Regulates the Malignant Characteristics of Oral Squamous Cell Carcinoma PossiblyFrontiers in oncology · 2021Article
- IL-21 Stimulates the expression and activation of cell cycle regulators and promotes cell proliferation in EBV-positive diffuse large B cell lymphoma.Scientific reports · 2020Article
- Prognostic value of novel immune-related genomic biomarkers identified in head and neck squamous cell carcinoma.Journal for immunotherapy of cancer · 2020Article
- Targeting tumors with IL-21 reshapes the tumor microenvironment by proliferating PD-1intTim-3-CD8+ T cells.JCI insight · 2020Article
- Interplay between HGAL and Grb2 proteins regulates B-cell receptor signaling.Blood advances · 2019Article
- Article
- Aberrant promoter methylation profiles and association with survival in patients with hepatocellular carcinoma.OncoTargets and therapy · 2017Article
- IL-21 Signaling in Immunity.F1000Research · 2016Review
- Lymphoma: immune evasion strategies.Cancers · 2015Review
- Adoptive Transfer of Interleukin-21-stimulated Human CD8+ T Memory Stem Cells Efficiently Inhibits Tumor Growth.Journal of immunotherapy (Hagerstown, Md. : 1997)Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Mantle cell lymphoma (MCL) is a distinct subtype of non-Hodgkin lymphoma characterized by overexpression of cyclin D1 in 95% of patients. MCL patients experience frequent relapses resulting in median survival of 3 to 5 years, requiring more efficient therapeutic regimens. Interleukin (IL)-21, a member of the IL-2 cytokine family, possesses potent antitumor activity against a variety of cancers not expressing the IL-21 receptor (IL-21R) through immune activation. Previously, we established that IL-21 exerts direct cytotoxicity on IL-21R-expressing diffuse large B-cell lymphoma cells. Herein, we demonstrate that IL-21 possesses potent cytotoxicity against MCL cell lines and primary tumors. We identify that IL-21-induced direct cytotoxicity is mediated through signal transducer and activator of transcription 3-dependent cMyc upregulation, resulting in activation of Bax and inhibition of Bcl-2 and Bcl-XL. IL-21-mediated cMyc upregulation is only observed in IL-21-sensitive cells. Further, we demonstrate that IL-21 leads to natural killer (NK)-cell-dependent lysis of MCL cell lines that were resistant to direct cytotoxicity. In vivo treatment with IL-21 results in complete FC-muMCL1 tumor regression in syngeneic mice via NK- and T-cell-dependent mechanisms. Together, these data indicate that IL-21 has potent antitumor activity against MCL cells via direct cytotoxic and indirect, immune-mediated effects.
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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.