Evidence map›Paper›PMID 35981475›Full record

ArticleBlood2022

GARP-mediated active TGF-β1 induces bone marrow NK cell dysfunction in AML patients with early relapse post-allo-HSCT.

Dongyao Wang, Zimin Sun, Xiaoyu Zhu, Xiaohu Zheng, Yonggang Zhou, Yichen Lu, Peidong Yan, Huiru Wang, Huilan Liu, Jing Jin and 6 more

Erratum issuedOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Blood, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
9.0field-weighted citation impact, top 1% 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

45 citing papers in PubMed, 61 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Review
  6. Review
  7. Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. Article
  13. The mouse resource at National Resource Center for Mutant Mice of China.Mammalian genome : official journal of the International Mammalian Genome Society · 2025
    Review
  14. Article
  15. Article
  16. Review
  17. Article
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 1 institution in 1 country.

Dongyao WangDivision of Life Sciences and Medicine, Department of Hematology, the First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, China.ORCID 0000-0003-1720-1135
Zimin SunDivision of Life Sciences and Medicine, Department of Hematology, the First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, China.
Xiaoyu ZhuDivision of Life Sciences and Medicine, Department of Hematology, the First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, China.
Xiaohu ZhengInstitute of Immunology, School of Basic Medicine and Medical Center, University of Science and Technology of China, Hefei, Anhui, China.
Yonggang ZhouInstitute of Immunology, School of Basic Medicine and Medical Center, University of Science and Technology of China, Hefei, Anhui, China.ORCID 0000-0003-2905-3213
Yichen LuInstitute of Immunology, School of Basic Medicine and Medical Center, University of Science and Technology of China, Hefei, Anhui, China.
Peidong YanInstitute of Immunology, School of Basic Medicine and Medical Center, University of Science and Technology of China, Hefei, Anhui, China.
Huiru WangDivision of Life Sciences and Medicine, Department of Hematology, the First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, China.
Huilan LiuDivision of Life Sciences and Medicine, Department of Hematology, the First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, China.
Jing JinInstitute of Immunology, School of Basic Medicine and Medical Center, University of Science and Technology of China, Hefei, Anhui, China.ORCID 0000-0003-3232-4141
Huaiping ZhuBlood and Cell Therapy Institute, Anhui Provincial Key Laboratory of Blood Research and Applications, University of Science and Technology of China, Hefei, Anhui, China.
Rui SunInstitute of Immunology, School of Basic Medicine and Medical Center, University of Science and Technology of China, Hefei, Anhui, China.
Yi WangInstitute of Immunology, School of Basic Medicine and Medical Center, University of Science and Technology of China, Hefei, Anhui, China.ORCID 0000-0003-0797-5209
Binqing FuInstitute of Immunology, School of Basic Medicine and Medical Center, University of Science and Technology of China, Hefei, Anhui, China.ORCID 0000-0002-7713-0001
Zhigang TianInstitute of Immunology, School of Basic Medicine and Medical Center, University of Science and Technology of China, Hefei, Anhui, China.
Haiming WeiDivision of Life Sciences and Medicine, Department of Hematology, the First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, China.
University of Science and Technology of China · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Relapse is a leading cause of death after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute myeloid leukemia (AML). However, the underlying mechanisms remain poorly understood. Natural killer (NK) cells play a crucial role in tumor surveillance and cancer immunotherapy, and NK cell dysfunction has been observed in various tumors. Here, we performed ex vivo experiments to systematically characterize the mechanisms underlying the dysfunction of bone marrow-derived NK (BMNK) cells isolated from AML patients experiencing early relapse after allo-HSCT. We demonstrated that higher levels of active transforming growth factor β1 (TGF-β1) were associated with impaired effector function of BMNK cells in these AML patients. TGF-β1 activation was induced by the overexpression of glycoprotein A repetitions predominant on the surface of CD4+ T cells. Active TGF-β1 significantly suppressed mTORC1 activity, mitochondrial oxidative phosphorylation, the proliferation, and cytotoxicity of BMNK cells. Furthermore, pretreatment with the clinical stage TGF-β1 pathway inhibitor, galunisertib, significantly restored mTORC1 activity, mitochondrial homeostasis, and cytotoxicity. Importantly, the blockade of the TGF-β1 signaling improved the antitumor activity of NK cells in a leukemia xenograft mouse model. Thus, our findings reveal a mechanism explaining BMNK cell dysfunction and suggest that targeted inhibition of TGF-β1 signaling may represent a potential therapeutic intervention to improve outcomes in AML patients undergoing allo-HSCT or NK cell-based immunotherapy.

Indexed as

Hematopoietic Stem Cell TransplantationLeukemia, Myeloid, AcuteAnimalsBone MarrowChronic DiseaseHumansKiller Cells, NaturalMiceRecurrenceTransforming Growth Factor beta1Transplantation, HomologousTransforming Growth Factor beta1

Identifiers

PMID35981475
PMCPMC10653097
OpenAlexW4293067750

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.