Evidence map›Paper›PMID 30451741›Full record

ArticleTransplantation2019

mTOR Inhibitor Everolimus in Regulatory T Cell Expansion for Clinical Application in Transplantation.

Roberto Gedaly, Felice De Stefano, Lilia Turcios, Marita Hill, Giovanna Hidalgo, Mihail I Mitov, Michael C Alstott, D Allan Butterfield, Hunter C Mitchell, Jeremy Hart and 3 more

Abstract read
In one paragraph

Article in Transplantation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.3field-weighted citation impact, top 11% 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

27 citing papers in PubMed, 35 citations in OpenAlex.

  1. Review
  2. Regulatory T cells in cancer and inflammation.Signal transduction and targeted therapy · 2026
    Review
  3. Article
  4. Article
  5. Review
  6. Review
  7. Receptor-Mediated SPION Labeling of CD4Nanomaterials (Basel, Switzerland) · 2025
    Article
  8. Effect of mitochondrial oxidative stress on regulatory T cell manufacturing for clinical application in transplantation: Results from a pilot study.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2025
    Article
  9. Review
  10. Review
  11. Article
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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 1 institution in 1 country.

Roberto GedalyTransplant Division, Department of Surgery, University of Kentucky, College of Medicine, Lexington, KY.
Felice De StefanoTransplant Division, Department of Surgery, University of Kentucky, College of Medicine, Lexington, KY.
Lilia TurciosTransplant Division, Department of Surgery, University of Kentucky, College of Medicine, Lexington, KY.
Marita HillDepartment of Pathology and Laboratory Medicine, University of Kentucky, College of Medicine, Lexington, KY.
Giovanna HidalgoDepartment of Pathology and Laboratory Medicine, University of Kentucky, College of Medicine, Lexington, KY.
Mihail I MitovRedox Metabolism (RM) Shared Resource Facility (SRF), Markey Cancer Center, University of Kentucky, College of Medicine, Lexington, KY.
Michael C AlstottRedox Metabolism (RM) Shared Resource Facility (SRF), Markey Cancer Center, University of Kentucky, College of Medicine, Lexington, KY.
D Allan ButterfieldRedox Metabolism (RM) Shared Resource Facility (SRF), Markey Cancer Center, University of Kentucky, College of Medicine, Lexington, KY.
Hunter C MitchellTransplant Division, Department of Surgery, University of Kentucky, College of Medicine, Lexington, KY.
Jeremy HartDepartment of Pathology and Laboratory Medicine, University of Kentucky, College of Medicine, Lexington, KY.
Ahmad Al-AttarDepartment of Pathology and Laboratory Medicine, University of Kentucky, College of Medicine, Lexington, KY.
Chester D JenningsDepartment of Pathology and Laboratory Medicine, University of Kentucky, College of Medicine, Lexington, KY.
Francesc MartiTransplant Division, Department of Surgery, University of Kentucky, College of Medicine, Lexington, KY.
Asbury University · US

Funding

University of Kentucky Markey Cancer Center Support Grant ECIA SupplementP30CA177558 · NCI · UNIVERSITY OF KENTUCKY · PI KATHLEEN L. O'CONNOR · 2013 to 2026
$38.3M
Kentucky Center for Clinical and Translational ScienceUL1TR001998 · NCATS · UNIVERSITY OF KENTUCKY · PI HARTMANN, KATHERINE E, KERN, PHILIP A · 2016 to 2025
$34.2M
Function and Stability of Expanded Regulatory T cells in Obese Renal Transplant CandidatesR03AI135592 · NIAID · UNIVERSITY OF KENTUCKY · PI MARTI, FRANCESC · 2018 to 2019
$153k
NCATS NIH HHS UL1 TR001998NCI NIH HHS P30 CA177558NIAID NIH HHS R03 AI135592
6 · The paper itself

Abstract

backgroundExperimental and preclinical evidence suggest that adoptive transfer of regulatory T (Treg) cells could be an appropriate therapeutic strategy to induce tolerance and improve graft survival in transplanted patients. The University of Kentucky Transplant Service Line is developing a novel phase I/II clinical trial with ex vivo expanded autologous Treg cells as an adoptive cellular therapy in renal transplant recipients who are using everolimus (EVR)-based immunosuppressive regimen.

methodsThe aim of this study was to determine the mechanisms of action and efficacy of EVR for the development of functionally competent Treg cell-based adoptive immunotherapy in transplantation to integrate a common EVR-based regimen in vivo (in the patient) and ex vivo (in the expansion of autologous Treg cells). CD25 Treg cells were selected from leukapheresis product with a GMP-compliant cell separation system and placed in 5-day (short) or 21-day (long) culture with EVR or rapamycin (RAPA). Multi-parametric flow cytometry analyses were used to monitor the expansion rates, phenotype, autophagic flux, and suppressor function of the cells. phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway profiles of treated cells were analyzed by Western blot and cell bioenergetic parameters by extracellular flux analysis.

resultsEVR-treated cells showed temporary slower growth, lower metabolic rates, and reduced phosphorylation of protein kinase B compared with RAPA-treated cells. In spite of these differences, the expansion rates, phenotype, and suppressor function of long-term Treg cells in culture with EVR were similar to those with RAPA.

conclusionsOur results support the feasibility of EVR to expand functionally competent Treg cells for their clinical use.

Indexed as

Organ TransplantationCells, CulturedEnergy MetabolismEverolimusFlow CytometryHumansImmunosuppressive AgentsImmunotherapy, AdoptiveMembrane Potential, MitochondrialSignal TransductionSirolimusT-Lymphocytes, RegulatoryTOR Serine-Threonine KinasesEverolimusImmunosuppressive AgentsSirolimusTOR Serine-Threonine Kinases

Identifiers

PMID30451741
PMCPMC6433536
OpenAlexW2901385086

What OpenQuestion holds

Textmetadata
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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.