ArticleOncotarget2016
Fas ligand and lytic granule differentially control cytotoxic dynamics of natural killer cell against cancer target.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis 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
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- Prognostic Significance of Tumor-Infiltrating Natural Killer Cells in Solid Tumors: A Systematic Review and Meta-Analysis.Frontiers in immunology · 2020Pooled it
- Natural Killer Cell Immunotherapy in Solid Tumors: Microenvironmental Obstacles and Translational 3D Models.Biology · 2026Review
- Tumor microenvironment-driven natural killer cell diversity: mechanisms and therapeutic opportunities.Cancer biology & medicine · 2026Review
- The p53 tumor suppressor modulates the expression of proteins that control natural killer cell activity.Cell communication and signaling : CCS · 2026Article
- Evolutionary Double-Bind Treatment Using Radiation Therapy and Natural Killer Cell-Based Immunotherapy in Prostate Cancer.International journal of radiation oncology, biology, physics · 2026Article
- Natural Killer Cell Phenotype and Function as a Predictive Factor for Treatment Response to Neoadjuvant Therapy in Breast Cancer Patients.International journal of molecular sciences · 2026Article
- Immune regulatory mechanisms in the tumor microenvironment and their applications in cancer therapy: from basic research to clinical translation.Frontiers in immunology · 2026Review
- NBMC medical genomics · 2025Article
- New approaches of chimeric antigen receptor (CAR)-immune cell-based therapy in gastric cancer; highlight CAR-T and CAR-NK.Functional & integrative genomics · 2025Review
- Comparison of the Cytotoxicity, Internalization and Anti-Cancer Drug Delivery Efficacy of Nature Killer Cell Derived Nanovesicles and Extracellular Vesicles.International journal of nanomedicine · 2025Article
- Natural Killer cells at the frontline in the fight against cancer.Cell death & disease · 2024Review
- An Improved Two-Shot Tracking Algorithm for Dynamics Analysis of Natural Killer Cells in Tumor Contexts.Bioengineering (Basel, Switzerland) · 2024Article
- Evolution of innate immunity: lessons from mammalian models shaping our current view of insect immunity.Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2024Review
- Hsp70, in Combination with IL-15 and PD-1 Blocker, Interferes with The Induction of Cytotoxic NK Cells in Relapsed Acute Myeloid Leukemia Patients.Cell journal · 2023Article
- Metformin promotes antitumor activity of NK cells via overexpression of miRNA-150 and miRNA-155.American journal of translational research · 2023Article
- Leveraging Natural Killer Cell Innate Immunity against Hematologic Malignancies: From Stem Cell Transplant to Adoptive Transfer and Beyond.International journal of molecular sciences · 2022Review
- [Progress in chimeric antigen receptor NK cell therapy for hematological malignancies].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2022Article
- Microfluidic live tracking and transcriptomics of cancer-immune cell doublets link intercellular proximity and gene regulation.Communications biology · 2022Article
- What Inhibits Natural Killers' Performance in Tumour.International journal of molecular sciences · 2022Review
- Locked and Loaded: Mechanisms Regulating Natural Killer Cell Lytic Granule Biogenesis and Release.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interaction dynamics between Natural Killer (NK) cells and cancer targets have been the topic of many previous investigations, but the underlying rate-limiting kinetics and heterogeneity remain poorly understood. In this study, using quantitative single cell microscopy assay, we elucidate the differential dynamic control of NK-cancer cell interaction by multiple cytotoxic pathways. We found primary human NK cell, unlike NK cell line, killed adherent cancer target mainly by lytic granule-independent mechanism, in particular through Fas ligand (FasL). And the distinct kinetics of FasL and lytic granule pathway resulted in significant cell-to-cell variability. Killing by FasL occurred slowly, requiring transient, often multiple NK-cancer cell conjugations that gradually activated caspase-8, while lytic granule triggered rapid cytotoxicity by a switch-like induction of granzyme-B upon a single, prolonged conjugation. Moreover, interleukin 2 was observed to enhance both cytotoxic mechanisms by promoting target recognition by NK cell and increasing NK-cancer cell interaction frequency. Our results not only identify the key points of variation in the rate-limiting kinetics of NK-cancer cell cytotoxic interaction but also point to the importance of non-lytic granule mechanism for developing NK cell therapy.
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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.