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Record W4412630273 · doi:10.1002/eji.70009

LAG3 Marks Activated but Hyporesponsive NK Cells

2025· article· en· W4412630273 on OpenAlexafffund
Valeria Vasilyeva, Olivia Makinson, Cynthia Chan, M. Park, Colin O’Dwyer, Ayad Ali, Abrar Ul Haq Khan, Christiano Tanese de Souza, Mohamed S. Hasim, Sara Asif, Reem Kurdieh, John Abou‐Hamad, Edward Yakubovich, Jonathan J. Hodgins, Patrick Haddad, Giuseppe Pietropaolo, Julija Mazej, Hobin Seo, Qiutong Huang, Sarah Nersesian, Damien Chay, Nicolas Jacquelot, David P. Cook, SeungHwan Lee, Giuseppe Sciumè, Stephen N. Waggoner, Michele Ardolino, Marie Marotel

Bibliographic record

VenueEuropean Journal of Immunology · 2025
Typearticle
Languageen
FieldImmunology and Microbiology
TopicImmune Cell Function and Interaction
Canadian institutionsAlberta Children's HospitalUniversity of CalgaryOttawa HospitalAlberta Cancer FoundationInstitute of Infection and ImmunityUniversity of Ottawa
FundersCumming School of Medicine, University of CalgaryCancer Council NSWHorizon 2020 Framework ProgrammeCanadian Institutes of Health ResearchAssociazione Italiana per la Ricerca sul CancroCanada Foundation for InnovationSocial Sciences and Humanities Research Council of CanadaMelanoma Research AllianceUniversity of TorontoUniversity of OttawaCanadian Cancer SocietyAlberta Cancer FoundationNational Institute of Allergy and Infectious DiseasesCancer Research SocietyCanadian Allergy, Asthma and Immunology FoundationOttawa Hospital Research InstituteH2020 Marie Skłodowska-Curie ActionsUniversity of Pittsburgh
KeywordsBiologyInterleukin 21TIGITInterleukin 12Immune systemImmunologyCytotoxic T cellCancer researchImmune checkpointIL-2 receptorZAP70NK-92ImmunosurveillanceCD8Cell biologyT cellImmunotherapyIn vitro

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.007
GPT teacher head0.213
Teacher spread0.206 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations5
Published2025
Admission routes2
Has abstractyes

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