Evidence map›Paper›PMID 32255769›Full record

ArticleJCI insight2020

Metabolic reprogramming augments potency of human pSTAT3-inhibited iTregs to suppress alloreactivity.

Kelly Walton, Mario R Fernandez, Elizabeth M Sagatys, Jordan Reff, Jongphil Kim, Marie Catherine Lee, John V Kiluk, Jane Yuet Ching Hui, David McKenna, Meghan Hupp and 11 more

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
0.9field-weighted citation impact, top 27% 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

12 citing papers in PubMed, 15 citations in OpenAlex.

  1. Review
  2. Article
  3. Immunometabolism of Liver Xenotransplantation and Prospective Solutions.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. Review
  9. Review
  10. Regulatory T Cells in GVHD Therapy.Frontiers in immunology · 2021
    Review
  11. Article
  12. Metabolic Pathways in Alloreactive T Cells.Frontiers in immunology · 2020
    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

21 authors at 6 institutions in 1 country.

Kelly WaltonDivision of Hematology, Oncology, and Transplantation, Department of Medicine, Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA.
Mario R FernandezDepartment of Tumor Biology.
Elizabeth M SagatysDepartment of Hematopathology and Laboratory Medicine.
Jordan ReffDepartment of Immunology.
Jongphil KimDepartment of Biostatistics and Bioinformatics, and.
Marie Catherine LeeDepartment of Breast Oncology, Moffitt Cancer Center, Tampa, Florida, USA.
John V KilukDepartment of Breast Oncology, Moffitt Cancer Center, Tampa, Florida, USA.
Jane Yuet Ching HuiDepartment of Surgery.
David McKennaDepartment of Laboratory Medicine and Pathology, and.
Meghan HuppDepartment of Laboratory Medicine and Pathology, and.
Colleen ForsterBionet Histology Research Laboratory, University of Minnesota, Minneapolis, Minnesota, USA.
Michael A LindenDepartment of Laboratory Medicine and Pathology, and.
Nicholas J LawrenceDepartment of Drug Discovery and.
Harshani R LawrenceDepartment of Drug Discovery and.
Joseph PidalaDepartment of Blood and Marrow Transplantation and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida, USA.
Steven Z PavleticCenter for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
Bruce R BlazarDivision of Blood and Marrow Transplantation, Department of Pediatrics, Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA.
Said M SebtiDepartment of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia USA.
John L ClevelandDepartment of Tumor Biology.
Claudio AnasettiDepartment of Blood and Marrow Transplantation and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida, USA.
Brian C BettsDivision of Hematology, Oncology, and Transplantation, Department of Medicine, Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA.
Moffitt Cancer Center · USEmory University Hospital · USUniversity of Minnesota Medical Center · USNational Cancer Institute · USUniversity of Minnesota · USVirginia Commonwealth University · US

Funding

Women's CancerP30CA077598 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Jeffrey S. Miller · 1998 to 2026
$100.4M
TRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI Christine O'Connell · 1998 to 2026
$93.5M
Trial Design and Biostatistical Support CoreP01CA065493 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI J SUNIL RAO · 1995 to 2026
$48.2M
Transgenic/KnockoutP01AI056299 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI BLAZAR, BRUCE R · 2003 to 2023
$42.5M
University of Minnesota Clinical and Translational Science Institute (UMN CTSI)UL1TR002494 · NCATS · UNIVERSITY OF MINNESOTA · PI BLAZAR, BRUCE R, WEISDORF, DANIEL J · 2018 to 2022
$34.9M
Project 3: Humoral Targets and B Cell Biology in Chronic Graft-vs.-Host DiseaseP01CA142106 · NCI · DANA-FARBER CANCER INST · PI RITZ, JEROME · 2009 to 2019
$17.5M
NIH Chronic GVHD Study GroupZIABC011743 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI PAVLETIC, STEVEN · 2016 to 2025
$10.2M
Enhancing Treg Therapeutic Efficacy in GVHDR01HL118979 · NHLBI · UNIVERSITY OF MINNESOTA · PI BLAZAR, BRUCE R, HIPPEN, KELI L · 2014 to 2025
$6.7M
T-CELL TARGETING FOR GVHDR01HL056067 · NHLBI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI BLAZAR, BRUCE R · 1995 to 2022
$5.4M
In Vivo Prevention of Murine GVHDR37AI034495 · NIAID · UNIVERSITY OF MINNESOTA · PI Bruce R Blazar · 2017 to 2026
$5.4M
Nongenotoxic conditioning for gene therapy and allogeneic transplantation in Fanconi anemiaR01HL147324 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Bruce R Blazar, HANS-PETER KIEM · 2020 to 2026
$4.1M
Exploiting the VISTA Pathway to Prevent Acute GVHD and Control Steroid Refractory DiseaseR01HL155114 · NHLBI · UNIVERSITY OF MINNESOTA · PI BLAZAR, BRUCE R, NOELLE, RANDOLPH J. · 2021 to 2024
$2.7M
NCATS NIH HHS UL1 TR002494NCI NIH HHS P01 CA065493NCI NIH HHS P01 CA142106NCI NIH HHS P30 CA076292NCI NIH HHS P30 CA077598NCI NIH HHS R50 CA211447NHLBI NIH HHS R01 HL056067NHLBI NIH HHS R01 HL118979NHLBI NIH HHS R01 HL133823NHLBI NIH HHS R01 HL147324NHLBI NIH HHS R01 HL155114NIAID NIH HHS P01 AI056299NIAID NIH HHS R37 AI034495
6 · The paper itself

Abstract

Immunosuppressive donor Tregs can prevent graft-versus-host disease (GVHD) or solid-organ allograft rejection. We previously demonstrated that inhibiting STAT3 phosphorylation (pSTAT3) augments FOXP3 expression, stabilizing induced Tregs (iTregs). Here we report that human pSTAT3-inhibited iTregs prevent human skin graft rejection and xenogeneic GVHD yet spare donor antileukemia immunity. pSTAT3-inhibited iTregs express increased levels of skin-homing cutaneous lymphocyte-associated antigen, immunosuppressive GARP and PD-1, and IL-9 that supports tolerizing mast cells. Further, pSTAT3-inhibited iTregs significantly reduced alloreactive conventional T cells, Th1, and Th17 cells implicated in GVHD and tissue rejection and impaired infiltration by pathogenic Th2 cells. Mechanistically, pSTAT3 inhibition of iTregs provoked a shift in metabolism from oxidative phosphorylation (OxPhos) to glycolysis and reduced electron transport chain activity. Strikingly, cotreatment with coenzyme Q10 restored OxPhos in pSTAT3-inhibited iTregs and augmented their suppressive potency. These findings support the rationale for clinically testing the safety and efficacy of metabolically tuned, human pSTAT3-inhibited iTregs to control alloreactive T cells.

Indexed as

Graft RejectionGraft vs Host DiseaseT-Lymphocytes, RegulatoryAnimalsHumansMiceOxidation-ReductionSTAT3 Transcription FactorSTAT3 protein, humanSTAT3 Transcription FactorImmunologySignal transductionStem cell transplantationT cellsTransplantation

Identifiers

PMID32255769
PMCPMC7253027
OpenAlexW3014836789

What OpenQuestion holds

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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.