Evidence map›Paper›PMID 26230954›Full record

ArticleBlood cancer journal2015

PD-1(hi)TIM-3(+) T cells associate with and predict leukemia relapse in AML patients post allogeneic stem cell transplantation.

Y Kong, J Zhang, D F Claxton, W C Ehmann, W B Rybka, L Zhu, H Zeng, T D Schell, H Zheng

2 registry-linked trialsOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Blood cancer journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 88 papers.

0numbers the graph read from it
0cells of the map it votes in
88citing papers in PubMed
5.0field-weighted citation impact, top 3% 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.

NCT03605589 phase1withdrawnnot on this mapstarted 2018, after this paper: background citation

A Pilot Study of Blinatumomab in Combination With a PD1 Inhibitor, Pembrolizumab, in Pediatric and Young Adult Patients With Relapsed/Refractory CD19 Positive B-cell Acute Leukemia or Lymphoma

TypeinterventionalSponsorChildren's Hospital Medical Center, CincinnatiRan2018 to 2022Enrolled0ConditionsLeukemia, B-cell, Lymphoma, B-CellArmsBlinatumomab, Pembrolizumab
NCT03964922 naunknown statusnot on this mapstarted 2019, after this paper: background citation

Study of the Immunoevasive Mecanisms and Especially Myeloid Suppressive Cells in the Medullar Microenvironment Employed by Myeloid Malignancy (AML and High Risk MDS) When Relapsing After Allogeneic Stem Cell Transplantation

TypeinterventionalSponsorCentral Hospital, Nancy, FranceRan2019 to 2022Enrolled104ConditionsRelapse Leukemia, Allogeneic Stem Cell Transplantation, Immune Evasion, TumorArmsblood sample, bone marrow sample
3 · Its place in the literature

Who cites it

88 citing papers in PubMed, 140 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Trial
  4. Over-expression of PD-1 Does Not Predict Leukemic Relapse after Allogeneic Stem Cell Transplantation.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2019
    Trial
  5. Review
  6. Review
  7. Article
  8. TIM-3 in AML: pathogenic roles and therapeutic targetability.Clinical and experimental medicine · 2026
    Review
  9. Review
  10. Review
  11. Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Review
  19. Review
  20. Article

28 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

9 authors at 2 institutions in 2 countries.

Y Kong1] Penn State Hershey Cancer Institute, Penn State University College of Medicine, Hershey, PA, USA [2] Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China.
J ZhangPenn State Hershey Cancer Institute, Penn State University College of Medicine, Hershey, PA, USA.
D F ClaxtonPenn State Hershey Cancer Institute, Penn State University College of Medicine, Hershey, PA, USA.
W C EhmannPenn State Hershey Cancer Institute, Penn State University College of Medicine, Hershey, PA, USA.
W B RybkaPenn State Hershey Cancer Institute, Penn State University College of Medicine, Hershey, PA, USA.
L Zhu1] Penn State Hershey Cancer Institute, Penn State University College of Medicine, Hershey, PA, USA [2] Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China.
H ZengInstitute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China.
T D Schell1] Penn State Hershey Cancer Institute, Penn State University College of Medicine, Hershey, PA, USA [2] Department of Microbiology and Immunology, Penn State University College of Medicine, Hershey, PA, USA.
H ZhengPenn State Hershey Cancer Institute, Penn State University College of Medicine, Hershey, PA, USA.
Penn State Milton S. Hershey Medical Center · USCapital Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Prognosis of leukemia relapse post allogeneic stem cell transplantation (alloSCT) is poor and effective new treatments are urgently needed. T cells are pivotal in eradicating leukemia through a graft versus leukemia (GVL) effect and leukemia relapse is considered a failure of GVL. T-cell exhaustion is a state of T-cell dysfunction mediated by inhibitory molecules including programmed cell death protein 1 (PD-1) and T-cell immunoglobulin domain and mucin domain 3 (TIM-3). To evaluate whether T-cell exhaustion and inhibitory pathways are involved in leukemia relapse post alloSCT, we performed phenotypic and functional studies on T cells from peripheral blood of acute myeloid leukemia patients receiving alloSCT. Here we report that PD-1(hi)TIM-3(+) cells are strongly associated with leukemia relapse post transplantation. Consistent with exhaustion, PD-1(hi)TIM-3(+) T cells are functionally deficient manifested by reduced production of interleukin 2 (IL-2), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). In addition, these cells demonstrate a phenotype consistent with exhausted antigen-experienced T cells by losing TN and TEMRA subsets. Importantly, increase of PD-1(hi)TIM-3(+) cells occurs before clinical diagnosis of leukemia relapse, suggesting their predictive value. Results of our study provide an early diagnostic approach and a therapeutic target for leukemia relapse post transplantation.

Indexed as

AgedBiomarkers, TumorCytokinesDisease-Free SurvivalFemaleHematopoietic Stem Cell TransplantationHepatitis A Virus Cellular Receptor 2HumansLeukemia, Myeloid, AcuteMaleMembrane ProteinsMiddle AgedNeoplasm Recurrence, LocalProgrammed Cell Death 1 ReceptorT-LymphocytesTransplantation, HomologousBiomarkers, TumorCytokinesHAVCR2 protein, humanHepatitis A Virus Cellular Receptor 2Membrane ProteinsPDCD1 protein, humanProgrammed Cell Death 1 Receptor

Identifiers

PMID26230954
PMCPMC4526784
OpenAlexW1544829530

What OpenQuestion holds

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LicenceCC BY
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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.