Evidence map›Paper›PMID 24806448›Full record

Trial reportCancer immunology, immunotherapy : CII2014

Interleukin-2-stimulated natural killer cells are less susceptible to mycophenolate mofetil than non-activated NK cells: possible consequences for immunotherapy.

Claudia Brehm, Sabine Huenecke, Ruth Esser, Stephan Kloess, Andrea Quaiser, Sibille Betz, Olga Zimmermann, Jan Soerensen, Jakob R Passweg, Thomas Klingebiel and 3 more

Open access · greenAbstract readClinical Trial, Phase IClinical Trial, Phase II
In one paragraph

Trial report in Cancer immunology, immunotherapy : CII, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

19 citing papers in PubMed, 28 citations in OpenAlex.

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  8. Distinct Effects of Immunosuppressive Drugs on the Anti-Pathogens (Basel, Switzerland) · 2019
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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

13 authors at 4 institutions in 2 countries.

Claudia BrehmClinic for Pediatric and Adolescent Medicine, University Hospital Frankfurt, Goethe University, Frankfurt/Main, Germany, Claudia.Brehm@kgu.de.
Sabine Huenecke
Ruth Esser
Stephan Kloess
Andrea Quaiser
Sibille Betz
Olga Zimmermann
Jan Soerensen
Jakob R Passweg
Thomas Klingebiel
Dirk Schwabe
Peter Bader
Ulrike Koehl
Goethe University Frankfurt · DEUniversity Hospital Frankfurt · DEMedizinische Hochschule Hannover · DEUniversity Hospital of Basel · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In a clinical phase I/II trial, pediatric patients with high-risk malignancies were treated with ex vivo IL-2-stimulated donor natural killer (NK) cells after transplantation with haploidentical stem cells. To evaluate the potential negative effects of the immunosuppressive drug mycophenolate mofetil (MMF) used for immunotherapy, the functionality and signaling of ex vivo NK cells was investigated. Our results show that during NK cell expansion, long-term (9 days) incubation with mycophenolic acid (MPA), the active metabolite of MMF, in therapeutically relevant concentrations led to the severe inhibition of NK cell proliferation. This correlated with a significantly reduced cytokine/chemokine secretion and the inhibited acquisition of surface receptors regarding cytotoxicity (e.g., NKp30, NKp44, NKp46, NKG2D), adhesion/migration (e.g., ICAM-1/CD54, LFA-1/CD11a, CD62L, CXCR3) and activation (e.g., CD25). Moreover, MPA prevented phosphorylation of the central signaling molecules STAT-3/-4/-5, AKT and ERK1/2. In contrast, short-term (24 h) MPA incubation of IL-2-stimulated NK cells had no or only marginal effects on the activated NK cell phenotype, including receptor expression, cytokine/chemokine secretion and intracellular signaling. Further, short-term MPA incubation only moderately affected the highly cytotoxic activity of previously IL-2-stimulated NK cells. In conclusion, while long-term MPA incubation significantly compromised ex vivo NK cell functionality, previously IL-2-activated NK cells seemed to be rather resistant to short-term MPA treatment. This finding supports the use of IL-2-activated NK cells as immunotherapy, especially for patients treated with MMF after haploidentical stem cell transplantation.

Indexed as

AdolescentCell Growth ProcessesChild, PreschoolEnzyme InhibitorsFemaleHumansImmunotherapy, AdoptiveInfantInterleukin-2Killer Cells, NaturalMaleMycophenolic AcidNeoplasmsEnzyme InhibitorsInterleukin-2Mycophenolic Acid

Identifiers

PMID24806448
PMCPMC11028798
OpenAlexW2168518154

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.