Evidence map›Paper›PMID 22972985›Full record

ArticleBlood2012

IFNγR signaling mediates alloreactive T-cell trafficking and GVHD.

Jaebok Choi, Edward D Ziga, Julie Ritchey, Lynne Collins, Julie L Prior, Matthew L Cooper, David Piwnica-Worms, John F DiPersio

Registry-linked trialOpen access · bronzeAbstract read
In one paragraph

Article in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07576699 (CK0802 for Treatment of Steroid Refractory Graft vs. Host Disease), which is not on this map. Cited by 95 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
95citing papers in PubMed, 1 pooled it
2.8field-weighted citation impact, top 9% 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.

NCT07576699 phase1 / phase2not yet recruitingnot on this mapstarted 2026, after this paper: background citation

CK0802 for Treatment of Steroid Refractory Graft vs. Host Disease (GVHD)

TypeinterventionalSponsorCellenkos, Inc.Ran2026 to 2029Enrolled12ConditionsSteroid Refractory Graft Versus Host DiseaseArmsCK0802 (Allogeneic, Cryopreserved, Cord blood-derived T-regulatory cells, cells that are not HLA matched)
3 · Its place in the literature

Who cites it

95 citing papers in PubMed, 1 synthesis or guideline pooled it, 147 citations in OpenAlex.

  1. Pooled it
  2. Trial
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  6. Article
  7. Article
  8. New age GVHD prophylaxis regimens: what works for what donor and why.Hematology. American Society of Hematology. Education Program · 2025
    Review
  9. Article
  10. Review
  11. Article
  12. Graft-Versus-Host Disease Mouse Models: A Clinical-Translational Perspective.Methods in molecular biology (Clifton, N.J.) · 2025
    Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review

35 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

8 authors at 1 institution in 1 country.

Jaebok ChoiDivision of Oncology, Department of Medicine, Washingtion University School of Medicine, St Louis, MO 63110, USA.
Edward D Ziga
Julie Ritchey
Lynne Collins
Julie L Prior
Matthew L Cooper
David Piwnica-Worms
John F DiPersio
Imaging Center · US

Funding

Specimen Acquistition and Expression ProfilingP01CA101937 · NCI · WASHINGTON UNIVERSITY · PI LEY, TIMOTHY J. · 2003 to 2023
$58.8M
WU-MDACC Inter-Institutional Molecular Imaging CenterP50CA094056 · NCI · WASHINGTON UNIVERSITY · PI KOPAN, RAPHAEL · 2002 to 2016
$26.3M
Genetic Manipulation of T Cells--PreClinical ModelsR01CA083845 · NCI · WASHINGTON UNIVERSITY · PI DIPERSIO, JOHN F · 2001 to 2005
$1.6M
TARGETING THE CXCR4-SDF1 AXIS AS THERAPY FOR RELAPSED/REFRACTORY AMLR21CA132269 · NCI · WASHINGTON UNIVERSITY · PI DIPERSIO, JOHN F. · 2009 to 2010
$669k
OPTIMIZING ALLOGENEIC TRANSPLANTATION USING CXCR4 BLOCKADER21CA141523 · NCI · WASHINGTON UNIVERSITY · PI DIPERSIO, JOHN F. · 2009 to 2010
$669k
DLI using genetically modified T cells: Phase 1 trialR21CA110489 · NCI · WASHINGTON UNIVERSITY · PI DIPERSIO, JOHN F · 2004 to 2005
$627k
NCI NIH HHS P01 CA101937NCI NIH HHS P50 CA094056NCI NIH HHS P50 CA94056NCI NIH HHS R01 CA083845NCI NIH HHS R01 CA83845NCI NIH HHS R21 CA110489NCI NIH HHS R21 CA132269NCI NIH HHS R21 CA141523
6 · The paper itself

Abstract

The clinical goal of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is to minimize GVHD while maintaining GvL. Here, we show that interferon γ receptor-deficient (IFNγR(-/-)) allogeneic Tconv, which possess normal alloreactivity and cytotoxicity, induce significantly less GVHD than wild-type (WT) Tconv. This effect is mediated by altered trafficking of IFNγR(-/-) Tconv to GVHD target organs, especially the gastrointestinal (GI) tract. We show that the chemokine receptor CXCR3 is induced via IFNγR-mediated signaling and partially contributes to the trafficking of WT Tconv to GVHD target organs. Indeed, CXCR3(-/-) Tconv recapitulate the reduced GVHD potential of IFNγR(-/-) Tconv in a minor-mismatched GVHD model. Most importantly, IFNγR(-/-) (and CXCR3(-/-)) Tconv mediate a robust and beneficial GvL effect. In addition, we show that IFNγR(-/-) regulatory T cells (Tregs) are fully suppressive in vitro although defective in suppressor function in vivo and that WT Tregs suppress GVHD in vivo only when allogeneic Tconv produce interferon γ (IFNγ), suggesting that the IFNγR signaling pathway is the major mechanism for both Tregs and Tconv to migrate to GVHD target organs. Finally, pharmacologic inhibition of IFNγR signaling with inhibitors of JAK1/JAK2, which are mediators of IFNγR signaling, results in the decreased expression of CXCR3 and reduced GVHD and improved survival after allo-HSCT and this effect is mediated by altered trafficking of Tconv to GVHD target organs.

Indexed as

Signal TransductionAnimalsAntigen-Presenting CellsCell MovementCells, CulturedGraft vs Host DiseaseHematopoietic Stem Cell TransplantationHumansInterferon gamma ReceptorJanus Kinase 1Janus Kinase 2MiceMice, TransgenicNitrilesPyrazolesPyrimidinesInterferon gamma ReceptorJanus Kinase 1Janus Kinase 2NitrilesPyrazolesPyrimidinesReceptors, CXCR3Receptors, Interferonruxolitinib

Identifiers

PMID22972985
PMCPMC3496960
OpenAlexW2144843164

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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.