ArticleLeukemia2021
Immunomodulatory drugs activate NK cells via both Zap-70 and cereblon-dependent pathways.
Article in Leukemia, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 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
37 citing papers in PubMed, 59 citations in OpenAlex.
- FTO promotes human NK cell proliferation yet restricts effector functions.Acta pharmacologica Sinica · 2026Article
- Single-nucleus RNA sequencing illuminates a functional analog of lymphoid organ in crustacean.Journal of advanced research · 2026Article
- KLRG1 silencing increases the efficacy of CAR NK cell therapy against colon cancer via SHP-2/ZAP-70/NF-κB signal pathway.Journal of translational medicine · 2026Article
- Xymedon Activates the Immune Response in Breast Cancer Xenografts.Biomedicines · 2025Article
- Differential substrate degradation by super-degron: EGFP in wild-type mouse cells, PD-1 requires CRBN humanization.iScience · 2025Article
- A phase 2 study of Daratumumab with Thalidomide and dexamethasone in relapsed and/or Refractory Myeloma (RRMM).Blood cancer journal · 2025Article
- Topical transdermal administration of lenalidomide nanosuspensions-based hydrogels against melanoma: In vitro and in vivo studies.International journal of pharmaceutics: X · 2025Article
- Identification of potent biparatopic antibodies targeting FGFR2 fusion-driven cholangiocarcinoma.The Journal of clinical investigation · 2025Article
- GPR132 regulates the function of NK cells through the Gαs/CSK/ZAP70/NF-κB signaling pathway as a potential immune checkpoint.Science advances · 2025Article
- Novel Therapies in Primary Central Nervous System Lymphoma.Clinical pharmacology : advances and applications · 2025Review
- Natural killer cell biology and therapy in multiple myeloma: challenges and opportunities.Experimental hematology & oncology · 2024Review
- Protein ubiquitination in ovarian cancer immunotherapy: The progress and therapeutic strategy.Genes & diseases · 2024Review
- Cytotoxic Programming of CD4+ T Cells Is Regulated by Opposing Actions of the Related Transcription Factors Eos and Aiolos.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Natural killer cells affect the natural course, drug resistance, and prognosis of multiple myeloma.Frontiers in cell and developmental biology · 2024Review
- Understanding NK cell biology for harnessing NK cell therapies: targeting cancer and beyond.Frontiers in immunology · 2023Review
- Therapeutic strategies to enhance immune response induced by multiple myeloma cells.Frontiers in immunology · 2023Review
- Review
- Review
- Harnessing natural killer cells for cancer immunotherapy: dispatching the first responders.Nature reviews. Drug discovery · 2022Review
- Natural killer cell awakening: unleash cancer-immunity cycle against glioblastoma.Cell death & disease · 2022Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Immunomodulatory drugs (IMiDs) lenalidomide and pomalidomide show remarkable antitumor activity in multiple myeloma (MM) via directly inhibiting MM-cell growth in the bone marrow (BM) microenvironment and promoting immune effector cell function. They are known to bind to the ubiquitin 3 ligase CRBN complex and thereby triggering degradation of IKZF1/3. In this study, we demonstrate that IMiDs also directly bind and activate zeta-chain-associated protein kinase-70 (Zap-70) via its tyrosine residue phosphorylation in T cells. IMiDs also triggered phosphorylation of Zap-70 in natural killer (NK) cells. Importantly, increased granzyme-B (GZM-B) expression and NK-cell activity triggered by IMiDs is associated with Zap-70 activation and inhibited by Zap-70 knockdown (KD), independent of CRBN. We also demonstrate a second mechanism whereby IMiDs trigger GZM-B and NK cytotoxicity which is CRBN and IKZF3 mediated, and inhibited or enhanced by KD of CRBN or IKZF3, respectively, independent of Zap-70. Our studies therefore show that IMiDs can enhance NK and T-cell cytotoxicity in (1) ZAP-70-mediated CRBN independent, as well as (2) CRBN-mediated ZAP-70 independent mechanisms; and provide the framework for developing novel therapeutics to activate Zap-70 and thereby enhance T and NK anti-MM cytotoxicity.
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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.