Evidence map›Paper›PMID 26002964›Full record

ArticleBlood2015

Lenalidomide augments actin remodeling and lowers NK-cell activation thresholds.

Kathryn Lagrue, Alex Carisey, David J Morgan, Rajesh Chopra, Daniel M Davis

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
87citing papers in PubMed, 1 pooled it
5.9field-weighted citation impact, top 3% of its field
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

87 citing papers in PubMed, 1 synthesis or guideline pooled it, 128 citations in OpenAlex.

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  4. AUGMENT: A Phase III Study of Lenalidomide Plus Rituximab Versus Placebo Plus Rituximab in Relapsed or Refractory Indolent Lymphoma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2019
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27 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 1 country.

Kathryn LagrueManchester Collaborative Centre for Inflammation Research, University of Manchester, Manchester, United Kingdom; Department of Life Sciences, Imperial College London, London, United Kingdom; and.
Alex CariseyManchester Collaborative Centre for Inflammation Research, University of Manchester, Manchester, United Kingdom;
David J MorganManchester Collaborative Centre for Inflammation Research, University of Manchester, Manchester, United Kingdom;
Rajesh ChopraDepartment of Translational Development, Celgene Corporation, Summit, NJ.
Daniel M DavisManchester Collaborative Centre for Inflammation Research, University of Manchester, Manchester, United Kingdom;
University of Manchester · GBCentre for Inflammation Research · GBImperial College London · GB

Funding

Biotechnology and Biological Sciences Research CouncilMedical Research Council G0500563Medical Research Council G1001044
6 · The paper itself

Abstract

As multiple myeloma (MM) progresses, natural killer (NK)-cell responses decline against malignant plasma cells. The immunomodulatory drug lenalidomide is widely used for treatment of MM but its influence on NK-cell biology is unclear. Here, we report that lenalidomide lowers the threshold for NK-cell activation, causing a 66% decrease in the 50% effective concentration (EC50) for activation through CD16, and a 38% decrease in EC50 for NK group 2 member D (NKG2D)-mediated activation, allowing NK cells to respond to lower doses of ligand. In addition, lenalidomide augments NK-cell responses, causing a twofold increase in the proportion of primary NK cells producing interferon-γ (IFN-γ), and a 20-fold increase in the amount of IFN-γ produced per cell. Importantly, lenalidomide did not trigger IFN-γ production in unstimulated NK cells. Thus, lenalidomide enhances the NK-cell arm of the immune response, without activating NK cells inappropriately. Of particular clinical importance, lenalidomide also allowed NK cells to be activated by lower doses of rituximab, an anti-CD20 monoclonal antibody (mAb) widely used to treat B-cell malignancies. This supports combined use of lenalidomide and rituximab in a clinical setting. Finally, superresolution microscopy revealed that lenalidomide increased the periodicity of cortical actin at immune synapses, resulting in an increase in the area of the actin mesh predicted to be penetrable to vesicles containing IFN-γ. NK cells from MM patients also responded to lenalidomide in this way. This indicates that nanometer-scale rearrangements in cortical actin, a recently discovered step in immune synapse assembly, are a potential new target for therapeutic compounds.

Indexed as

Actin CytoskeletonActinsCells, CulturedGPI-Linked ProteinsHumansImmunological SynapsesInterferon-gammaKiller Cells, NaturalLenalidomideLymphocyte ActivationLymphocyte CountNK Cell Lectin-Like Receptor Subfamily KReceptors, IgGThalidomideActinsFCGR3B protein, humanGPI-Linked ProteinsInterferon-gammaKLRK1 protein, humanLenalidomideNK Cell Lectin-Like Receptor Subfamily KReceptors, IgGThalidomide

Identifiers

PMID26002964
PMCPMC4551357
OpenAlexW1591236327

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.