Evidence map›Paper›PMID 40966288›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2025

Nanoscale restructuring of the immune synapse with an engager enhances NK cell function.

Khodor S Hazime, Sam Sheppard, Olatz Niembro-Vivanco, Cathal Hosty, Heather Thomas, Christopher Loosbroock, Leanne Peiser, Daniel M Davis

Erratum issuedAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Khodor S HazimeDepartment of Life Sciences, Sir Alexander Fleming Building, Imperial College London, South Kensington, London SW7 2AZ, United Kingdom.
Sam SheppardDepartment of Life Sciences, Sir Alexander Fleming Building, Imperial College London, South Kensington, London SW7 2AZ, United Kingdom.ORCID 0000-0002-1420-6910
Olatz Niembro-VivancoDepartment of Life Sciences, Sir Alexander Fleming Building, Imperial College London, South Kensington, London SW7 2AZ, United Kingdom.ORCID 0000-0003-2661-576X
Cathal HostyDepartment of Life Sciences, Sir Alexander Fleming Building, Imperial College London, South Kensington, London SW7 2AZ, United Kingdom.ORCID 0000-0002-5080-6665
Heather ThomasImmuno-Oncology Cellular Therapy Thematic Research Center, Bristol Myers Squibb, Seattle, WA 98109.
Christopher LoosbroockImmuno-Oncology Cellular Therapy Thematic Research Center, Bristol Myers Squibb, Seattle, WA 98109.ORCID 0009-0006-2258-2197
Leanne PeiserImmuno-Oncology Cellular Therapy Thematic Research Center, Bristol Myers Squibb, Seattle, WA 98109.
Daniel M DavisDepartment of Life Sciences, Sir Alexander Fleming Building, Imperial College London, South Kensington, London SW7 2AZ, United Kingdom.ORCID 0000-0002-9182-291X

Funding

UKRI | Medical Research Council (MRC) MR/W031698/1Wellcome TrustWellcome Trust (WT) 110091/Z/15/Z
6 · The paper itself

Abstract

Engagers are antibody-based therapies which bind immune cell receptors and a target cell ligand. Next-gen engagers typically bind two activating receptors, but the effect of this on immune synapse formation and signaling is unknown. Here, we coligated activating receptors CD16a and NKG2D on natural killer (NK) cells with a CD33-binding anti-acute myeloid leukemia (AML) engager. Superresolution microscopy revealed that coligating CD16a and NKG2D with a single molecule triggered their nanoscale coclustering. This enhanced phosphorylation of CD3ζ, ZAP70, and SLP-76 which augmented secretion of IFN-γ and TNF-α, by NK cells from healthy donors and AML patients. Thus, in addition to connecting immune cells to target cells, the clinical promise of engagers results from their ability to manipulate the nanoscale architecture of the immune synapse.

Indexed as

Immunological SynapsesKiller Cells, NaturalHumansInterferon-gammaLeukemia, Myeloid, AcuteNK Cell Lectin-Like Receptor Subfamily KPhosphorylationReceptors, IgGSialic Acid Binding Ig-like Lectin 3Signal TransductionTumor Necrosis Factor-alphaCD33 protein, humanInterferon-gammaKLRK1 protein, humanNK Cell Lectin-Like Receptor Subfamily KReceptors, IgGSialic Acid Binding Ig-like Lectin 3Tumor Necrosis Factor-alphaimmune synapsenatural killer cellsNKG2Dreceptor clusteringsuperresolution microscopy

Identifiers

PMID40966288
PMCPMC12478185

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

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.