Evidence map›Paper›PMID 40705324›Full record

ArticleEuropean journal of immunology2025

LAG3 Marks Activated but Hyporesponsive NK Cells.

Valeria Vasilyeva, Olivia Makinson, Cynthia Chan, Maria Park, Colin O'Dwyer, Ayad Ali, Abrar Ul Haq Khan, Christiano Tanese de Souza, Mohamed S Hasim, Sara Asif and 18 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European journal of immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
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

5 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
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

28 authors.

Valeria VasilyevaCancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
Olivia MakinsonCancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
Cynthia ChanCancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
Maria ParkCancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
Colin O'DwyerCancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
Ayad AliCenter For Autoimmune Genomics and Etiology, Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Abrar Ul Haq KhanDepartment of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada.
Christiano Tanese de SouzaCancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
Mohamed S HasimCancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada.ORCID 0000-0002-0275-3378
Sara AsifCancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
Reem KurdiehCancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
John Abou-HamadCancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
Edward YakubovichCancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
Jonathan HodginsCancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
Paul Al HaddadCancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
Giuseppe PietropaoloIRCCS Neuromed, Pozzilli, Italy.
Julija MazejDepartment of Molecular Medicine, Sapienza University of Rome, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci-Bolognetti, Rome, Italy.
Hobin SeoDepartment of Biochemistry & Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.ORCID 0009-0000-4651-7775
Qiutong HuangDepartment of Biochemistry & Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Sarah NersesianCancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
Damien ChayConsultant, Qweeble, Montreveault, France.
Nicolas JacquelotDepartment of Biochemistry & Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
David CookCancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
Seung-Hwan LeeDepartment of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada.
Giuseppe SciumèDepartment of Molecular Medicine, Sapienza University of Rome, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci-Bolognetti, Rome, Italy.ORCID 0000-0003-0131-512X
Stephen WaggonerCenter For Autoimmune Genomics and Etiology, Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Michele ArdolinoCancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada.ORCID 0000-0003-4114-0985
Marie MarotelCancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada.ORCID 0000-0002-1618-7602

Funding

Targeting natural killer cells to enhance HIV vaccine responsesR01AI148080 · NIAID · CINCINNATI CHILDRENS HOSP MED CTR · PI WAGGONER, STEPHEN N. · 2019 to 2023
$3.3M
Canada Foundation for Innovation #44762 to N.JCanadian Cancer Society grant #708072 to N.JItalian Association for Cancer Research IG-28719NIAID NIH HHS R01 AI148080
6 · The paper itself

Abstract

NK cells are critical for immunosurveillance, yet become dysfunctional when chronically stimulated by virally infected or cancerous cells. This phenomenon is similar to T cell exhaustion but less characterized, limiting therapeutic interventions. As shown for T cells, NK cells often display an increased expression of immune checkpoint proteins (ICP) following chronic stimulation, and ICP blockade therapies are currently being explored for several cancer types, with remarkable patient benefits. Nevertheless, the nature of ICP expression in NK cells is still poorly documented. In this study, we aimed to identify the conditions that lead to and the phenotype of immune checkpoint LAG3-expressing NK cells. Using various experimental models, we found that LAG3 is expressed by murine NK cells upon activation in different contexts, including in response to cancer and acute viral infections. LAG3 marks a subset of immature, proliferating, and activated cells, which, despite activation, have a reduced capacity to respond to a broad range of stimuli. Further characterization also revealed that LAG3+ NK cells exhibit a transcriptional signature similar to that of exhausted CD8+ T cells. Taken together, our results support the use of LAG3 as a marker of dysfunctional NK cells across diverse chronic and acute inflammatory conditions.

Indexed as

Antigens, CDKiller Cells, NaturalLymphocyte ActivationAnimalsCD8-Positive T-LymphocytesHumansLymphocyte Activation Gene 3 ProteinMiceMice, Inbred C57BLNeoplasmsAntigens, CDLag3 protein, mouseLymphocyte Activation Gene 3 Protein

Identifiers

PMID40705324
PMCPMC12288813

What OpenQuestion holds

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Registered trials

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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.