Evidence map›Paper›PMID 29339767›Full record

ArticleNature communications2018

Regulatory T cells trigger effector T cell DNA damage and senescence caused by metabolic competition.

Xia Liu, Wei Mo, Jian Ye, Lingyun Li, Yanping Zhang, Eddy C Hsueh, Daniel F Hoft, Guangyong Peng

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 139 papers.

0numbers the graph read from it
0cells of the map it votes in
139citing papers in PubMed
7.6field-weighted citation impact, top 2% 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

139 citing papers in PubMed, 219 citations in OpenAlex.

  1. Review
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  4. Pre-Encoded IFN-I Sensitivity Exacerbates Memory T Cell Senescence in Solid Tumors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  5. Review
  6. CD8Science China. Life sciences · 2026
    Review
  7. IL-15 Plus Thymosin α1 Reduces Senescent Hepatic CD8Journal of gastroenterology and hepatology · 2026
    Article
  8. Article
  9. Article
  10. Review
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  20. The diversity of CD8Nature reviews. Immunology · 2025
    Review

79 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.

Xia LiuDepartment of Internal Medicine, Division of Infectious Diseases, Allergy & Immunology, Saint Louis University School of Medicine, St Louis, MO, 63104, USA.
Wei MoDepartment of Internal Medicine, Division of Infectious Diseases, Allergy & Immunology, Saint Louis University School of Medicine, St Louis, MO, 63104, USA.
Jian YeDepartment of Internal Medicine, Division of Infectious Diseases, Allergy & Immunology, Saint Louis University School of Medicine, St Louis, MO, 63104, USA.
Lingyun LiDepartment of Internal Medicine, Division of Infectious Diseases, Allergy & Immunology, Saint Louis University School of Medicine, St Louis, MO, 63104, USA.
Yanping ZhangDepartment of Surgery, Division of General Surgery, Saint Louis University School of Medicine, St Louis, MO, 63110, USA.
Eddy C HsuehDepartment of Surgery, Division of General Surgery, Saint Louis University School of Medicine, St Louis, MO, 63110, USA.
Daniel F HoftDepartment of Internal Medicine, Division of Infectious Diseases, Allergy & Immunology, Saint Louis University School of Medicine, St Louis, MO, 63104, USA.
Guangyong PengDepartment of Internal Medicine, Division of Infectious Diseases, Allergy & Immunology, Saint Louis University School of Medicine, St Louis, MO, 63104, USA. guangyong.peng@health.slu.edu.ORCID http://orcid.org/0000-0001-7268-0234
Saint Louis University · US

Funding

Gamma/Delta Treg Cells and Human Breast CancerR01CA184379 · NCI · SAINT LOUIS UNIVERSITY · PI PENG, GUANGYONG · 2015 to 2019
$1.7M
T Regulatory Cells and Neonatal Innate ImmunityR21AI094478 · NIAID · SAINT LOUIS UNIVERSITY · PI KOENIG, JOYCE MARIE, PENG, GUANGYONG · 2012 to 2013
$413k
Commitment and Plasticity of Th17 cells and Tregs in the Tumor MicroenvironmentR21AI097852 · NIAID · SAINT LOUIS UNIVERSITY · PI PENG, GUANGYONG · 2012 to 2013
$413k
NCI NIH HHS R01 CA184379NIAID NIH HHS R21 AI094478NIAID NIH HHS R21 AI097852
6 · The paper itself

Abstract

Defining the suppressive mechanisms used by regulatory T (Treg) cells is critical for the development of effective strategies for treating tumors and chronic infections. The molecular processes that occur in responder T cells that are suppressed by Treg cells are unclear. Here we show that human Treg cells initiate DNA damage in effector T cells caused by metabolic competition during cross-talk, resulting in senescence and functional changes that are molecularly distinct from anergy and exhaustion. ERK1/2 and p38 signaling cooperate with STAT1 and STAT3 to control Treg-induced effector T-cell senescence. Human Treg-induced T-cell senescence can be prevented via inhibition of the DNA damage response and/or STAT signaling in T-cell adoptive transfer mouse models. These studies identify molecular mechanisms of human Treg cell suppression and indicate that targeting Treg-induced T-cell senescence is a checkpoint for immunotherapy against cancer and other diseases associated with Treg cells.

Indexed as

DNA DamageMAP Kinase Signaling SystemCellular SenescenceGlucoseHumansImmunotherapySTAT1 Transcription FactorSTAT3 Transcription FactorT-Lymphocytes, RegulatoryGlucoseSTAT1 protein, humanSTAT1 Transcription FactorSTAT3 protein, humanSTAT3 Transcription Factor

Identifiers

PMID29339767
PMCPMC5770447
OpenAlexW2782893319

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.