ArticleJournal of immunology (Baltimore, Md. : 1950)2021
Cbl-b Is Upregulated and Plays a Negative Role in Activated Human NK Cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
- Immunophenotypic Profiling of Lymphocyte Subsets in Children and Adolescents With Acute Lymphoblastic Leukaemia: Immune Dysregulation Before and After Remission.Journal of immunology research · 2026Article
- Natural killer cell-based immunotherapy for cancer.Journal of immunology (Baltimore, Md. : 1950) · 2025Review
- Mechanisms of Cbl-Mediated Ubiquitination of Proteins in T and Natural Killer Cells and Effects on Immune Cell Functions.Life (Basel, Switzerland) · 2024Review
- Inhibition of Cbl-b restores effector functions of human intratumoral NK cells.Journal for immunotherapy of cancer · 2024Article
- E3 ubiquitin ligase CBLB regulates innate immune responses and bacterial dissemination during nontuberculous mycobacteria infection.Journal of leukocyte biology · 2024Article
- Single cell transcriptomics shows that malaria promotes unique regulatory responses across multiple immune cell subsets.Nature communications · 2023Article
- CRISPR-Cas9-Based Gene Knockout of Immune Checkpoints in Expanded NK Cells.International journal of molecular sciences · 2023Article
- Renal cell carcinoma escapes NK cell-mediated immune surveillance through the downregulation of DNAM-1.Cancer communications (London, England) · 2023Article
- Harnessing IL-15 signaling to potentiate NK cell-mediated cancer immunotherapy.Trends in immunology · 2022Review
- Lipid accumulation induced by APOE4 impairs microglial surveillance of neuronal-network activity.Cell stem cell · 2022Article
- Hijacking TYRO3 from Tumor Cells via Trogocytosis Enhances NK-cell Effector Functions and Proliferation.Cancer immunology research · 2021Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
The E3 ubiquitin ligase Cbl-b has been characterized as an intracellular checkpoint in T cells; however, the function of Cbl-b in primary human NK cells, an innate immune anti-tumor effector cell, is not well defined. In this study, we show that the expression of Cbl-b is significantly upregulated in primary human NK cells activated by IL-15, IL-2, and the human NK cell-sensitive tumor cell line K562 that lacks MHC class I expression. Pretreatment with JAK or AKT inhibitors prior to IL-15 stimulation reversed Cbl-b upregulation. Downregulation of Cbl-b resulted in significant increases in granzyme B and perforin expression, IFN-γ production, and cytotoxic activity against tumor cells. Collectively, we demonstrate upregulation of Cbl-b and its inhibitory effects in IL-15/IL-2/K562-activated human NK cells, suggesting that Cbl-b plays a negative feedback role in human NK cells.
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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.