ArticleThe Journal of cell biology2018
Shedding of CD16 disassembles the NK cell immune synapse and boosts serial engagement of target cells.
Article in The Journal of cell biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers.
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Who cites it
121 citing papers in PubMed, 160 citations in OpenAlex.
- Identifying SARS-CoV-2 'memory' NK cells from COVID-19 convalescent donors for adoptive cell therapy.Immunology · 2022Trial
- Plasma membrane order maps functional diversity in immune cells.Nature chemical biology · 2026Article
- Assessment of Natural Killer Cell Serial Degranulation.Current protocols · 2026Article
- Review
- EGFRxCD16 bispecific antibodies orchestrate superior NK cell-mediated lysis of ovarian cancer and NSCLC cell lines in combination with oncolytic viruses.Cancer immunology, immunotherapy : CII · 2026Article
- CD56bioRxiv : the preprint server for biology · 2026Article
- The natural killer-cellular humoral activation test as a functional biomarker of antibody-mediated rejection after kidney transplantation.Scientific reports · 2026Article
- NKG2A+ NK cell cytotoxicity of Epstein-Barr virus infected B cells is mediated through the NKG2D and NKp30 activating receptors.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Discovery and preclinical evaluation of monoclonal antibodies and bispecific engagers targeting the NKG2A inhibitory receptor.Science advances · 2026Article
- Resident CD49aScience advances · 2026Article
- Dual-functioning Targeted ADAM17 Blocker CD16 (TAB16) mediates selective ADAM17 inhibition in NK cells and engages overexpressed ADAM17 in tumor cells to induce cytotoxicity.Frontiers in immunology · 2026Article
- Insights into ectodomain shedding as a novel target in natural killer cell-based immunotherapy for cancer.Frontiers in immunology · 2026Review
- CD38+ NK cells: novel players in immunoregulation.Frontiers in immunology · 2026Review
- Engineered neutrophil engagers overcome IgA limitations and reprogram resting neutrophils for cancer immunotherapy.Journal of biological engineering · 2025Article
- Avelumab induces greater Fc-Fc receptor-dependent natural killer cell activation and dendritic cell crosstalk compared to durvalumab.Oncoimmunology · 2025Article
- An Fc-Engineered Glycomodified Antibody Supports Proinflammatory Activation of Immune Effector Cells and Restricts Progression of Breast Cancer.Cancer research · 2025Article
- A monoclonal antibody that inhibits the shedding of CD16a and CD16b and promotes antibody-dependent cellular cytotoxicity against tumors.Nature communications · 2025Article
- Phenotypic, proteomic, and functional analyses of cytokine-induced memory-like NK cells show two distinct subsets based on CD16 expression.Scientific reports · 2025Article
- CD16A Shedding Regulates Innate Cell Engager-Induced Serial Killing by Natural Killer Cells.European journal of immunology · 2025Article
- Review
61 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Natural Killer (NK) cells can engage multiple virally infected or tumor cells sequentially and deliver perforin for cytolytic killing of these targets. Using microscopy to visualize degranulation from individual NK cells, we found that repeated activation via the Fc receptor CD16 decreased the amount of perforin secreted. However, perforin secretion was restored upon subsequent activation via a different activating receptor, NKG2D. Repeated stimulation via NKG2D also decreased perforin secretion, but this was not rescued by stimulation via CD16. These different outcomes of sequential stimulation could be accounted for by shedding of CD16 being triggered by cellular activation. The use of pharmacological inhibitors and NK cells transfected to express a noncleavable form of CD16 revealed that CD16 shedding also increased NK cell motility and facilitated detachment of NK cells from target cells. Disassembly of the immune synapse caused by CD16 shedding aided NK cell survival and boosted serial engagement of target cells. Thus, counterintuitively, shedding of CD16 may positively impact immune responses.
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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.