ArticleThe Journal of experimental medicine2019
NK cells switch from granzyme B to death receptor-mediated cytotoxicity during serial killing.
Article in The Journal of experimental medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 230 papers, 2 of them syntheses that pooled it.
What it found
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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
230 citing papers in PubMed, 2 syntheses or guidelines pooled it, 348 citations in OpenAlex.
- The soldiers needed to be awakened: Tumor-infiltrating immune cells.Frontiers in genetics · 2022Pooled it
- CD56-negative NK cells: Frequency in peripheral blood, expansion during HIV-1 infection, functional capacity, and KIR expression.Frontiers in immunology · 2022Pooled it
- Radiotherapy and DNA damage response inhibitors modestly sensitize HNSCC to NK cell killing, with ATM inhibition more effective than ATR inhibition.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2026Article
- Natural killer cells in ovarian cancer therapy: mechanisms, evasion, and therapeutic innovations.Inflammopharmacology · 2026Review
- Assessment of Natural Killer Cell Serial Degranulation.Current protocols · 2026Article
- Development of Chimeric Antigen Receptor-Modified NK Cells for the Immunotherapy of Adult T-Cell Leukemia/Lymphoma.European journal of haematology · 2026Article
- From single cell analysis to 3D micro physiological systems: microfluidic tools integrating cancer cell targets for delineating natural killer cell biology.Microsystems & nanoengineering · 2026Review
- Alterations in NK cell subsets and the regulatory role of JAB1 in nasopharyngeal carcinoma with implications for tumor immunity and biomarker development.British journal of cancer · 2026Article
- NK cell cytotoxicity is transiently enhanced during acute malaria and modulated by the host microenvironment.JCI insight · 2026Article
- Broadening activity of checkpoint blockade agents by intratumoral nucleoside cleavage.JCI insight · 2026Article
- [Fecal microbiota transplantation inhibits colonic tumor growth in mice by suppressing the TLR4/MyD88/NF-κB signaling pathway].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- YTHDF2 in inflammation: Mechanisms and therapeutic strategies.Genes & diseases · 2026Review
- Ex vivo-expanded allogeneic Vδ2 T cells specifically reduce reservoirs of HIV-1 following latency reversal.JCI insight · 2026Article
- A framework integrating multiscale in silico modeling and experimental data predicts CAR-NK cell cytotoxicity across target cell types.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Trojan Horse Strategy: How Biomimetic Nanomedicine Remodels the Tumor Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- T-Cell-Derived Exosomes From Multi Core Granules Exhibit Superior Caspase-3-Mediated Tumor-Suppressive Activity Compared to Those From Multivesicular Bodies.Journal of extracellular vesicles · 2026Article
- Exosomes in Cancer Biology: Emerging Biomarkers and Therapeutic Targets.Journal of Cancer · 2026Review
- CAF-derived BHB modulates FXR1-Kbhb and NK-cell lipid metabolism in osteosarcoma.International journal of biological sciences · 2026Article
- Targeting innate immunity in cancer: mechanistic foundations, therapeutic vaccination, and clinical translation.Frontiers in immunology · 2026Review
- A new era in CAR-NK cell therapy: from technological innovations to clinical applications.World journal of pediatrics : WJP · 2026Review
170 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
NK cells eliminate virus-infected and tumor cells by releasing cytotoxic granules containing granzyme B (GrzB) or by engaging death receptors that initiate caspase cascades. The orchestrated interplay between both cell death pathways remains poorly defined. Here we simultaneously measure the activities of GrzB and caspase-8 in tumor cells upon contact with human NK cells. We observed that NK cells switch from inducing a fast GrzB-mediated cell death in their first killing events to a slow death receptor-mediated killing during subsequent tumor cell encounters. Target cell contact reduced intracellular GrzB and perforin and increased surface-CD95L in NK cells over time, showing how the switch in cytotoxicity pathways is controlled. Without perforin, NK cells were unable to perform GrzB-mediated serial killing and only killed once via death receptors. In contrast, the absence of CD95 on tumor targets did not impair GrzB-mediated serial killing. This demonstrates that GrzB and death receptor-mediated cytotoxicity are differentially regulated during NK cell serial killing.
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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.