Evidence map›Paper›PMID 40289708›Full record

ArticleClinical and experimental immunology2025

Pharmacodynamic effect of mTOR inhibition-based immunosuppressive therapy on dendritic cell and natural killer cell subsets after renal transplantation.

Sabine Weber, Xinyi Wei, Guixia Chen, Katharina Yankouskaya, Decheng Yin, Ida Allabauer, Tilman Jobst-Schwan, Michael Wiesener, Mario Schiffer, Diana Dudziak and 3 more

Abstract read
In one paragraph

Article in Clinical and experimental immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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.

Sabine WeberPediatric Gastroenterology and Hepatology, Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
Xinyi WeiPediatric Gastroenterology and Hepatology, Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.ORCID 0009-0004-4573-446X
Guixia ChenPediatric Gastroenterology and Hepatology, Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
Katharina YankouskayaPediatric Gastroenterology and Hepatology, Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
Decheng YinPediatric Gastroenterology and Hepatology, Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
Ida AllabauerPediatric Gastroenterology and Hepatology, Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
Tilman Jobst-SchwanDepartment of Nephrology and Hypertension, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
Michael WiesenerDepartment of Nephrology and Hypertension, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
Mario SchifferDepartment of Nephrology and Hypertension, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
Diana DudziakInstitute of Immunology, Friedrich-Schiller-University Jena, Jena University Hospital, Jena, Germany.
Christian H K LehmannPediatric Gastroenterology and Hepatology, Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
Joachim WoelflePediatric Gastroenterology and Hepatology, Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
André HoerningPediatric Gastroenterology and Hepatology, Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.ORCID 0000-0001-6241-7168

Funding

Chinese Scholarship Council # 202208080310German Research Foundation # 509149993Robert-Pfleger Stiftung, Bamberg, Germany
6 · The paper itself

Abstract

backgroundmTOR inhibitor therapy is solely monitored via pharmacokinetics after kidney transplantation, which may not accurately reflect the effectiveness of PI3K-Akt-mTOR pathway blockade, potentially leading to inadequate or excessive immunosuppression. The pharmacodynamic effect of mTOR inhibition on natural killer (NK) cells and dendritic cell (DC) subsets after renal transplantation has not been investigated so far.

methodsPhosphoflow cytometry was employed in this cross-sectional study to evaluate the extent of mTOR inhibition in peripheral DC and NK cell subsets by assessing p70S6 kinase phosphorylation in kidney transplant recipients treated with mTOR inhibitors either in combination with calcineurin inhibitors (mTORi + CNI, n = 17) or mycophenolate sodium (mTORi + MPA, n = 9). The control group comprised nine end-stage renal disease patients undergoing dialysis therapy and 17 healthy volunteers.

resultsmTOR inhibitor-based therapy significantly reduced p70S6K phosphorylation levels in CD3-CD56+ NK cells compared to healthy controls, while p70S6K phosphorylation among HLA-DR+ Lin- total DCs was not different. In comparison to mTORi + MPA therapy, renal transplant patients receiving mTORi + CNI treatment exhibited a stronger inhibition of p70S6K phosphorylation in HLA-DR+ Lin- total DCs, CD123+CD11c- plasmacytoid DCs, CD123-CD11c+ myeloid DCs, and CD16-CD56bright NK cells. However, the serum trough levels of mTORi showed no correlation with p70S6K phosphorylation levels in all investigated cell subsets.

conclusionmTORi selectively suppressed p70S6K phosphorylation in specific DC and NK subtypes. Evaluating p70S6K phosphorylation through phosphoflow cytometry might serve as a clinically applicable method to comprehend immune cell subset-specific effects of mTOR inhibition, providing detailed pharmacodynamic insights for tailoring mTORi therapy on an individual basis.

Indexed as

Dendritic CellsImmunosuppressive AgentsKidney TransplantationKiller Cells, NaturalMTOR InhibitorsTOR Serine-Threonine KinasesAdultAgedCalcineurin InhibitorsCross-Sectional StudiesFemaleHumansImmunosuppression TherapyMaleMiddle AgedMycophenolic AcidCalcineurin InhibitorsImmunosuppressive AgentsMTOR InhibitorsMTOR protein, humanMycophenolic AcidRibosomal Protein S6 Kinases, 70-kDaTOR Serine-Threonine Kinasescalcineurin inhibitorsdendritic cellskidney transplantationmTORiNK cellsp70S6 kinasephosphoflow cytometry

Identifiers

PMID40289708
PMCPMC12094924

What Socratic holds

Textmetadata
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Registered trials

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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 Socratic graph.