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Record W4386033544 · doi:10.1038/s42255-023-00855-2

Glutarate regulates T cell metabolism and anti-tumour immunity

2023· article· en· W4386033544 on OpenAlexfundno aff
Eleanor Minogue, Pedro P. Cunha, Brennan J. Wadsworth, Guinevere L. Grice, Shiv K. Sah‐Teli, R. J. F. Hughes, David Bargiela, Alessandro Quaranta, Javier Zurita, Robin Antrobus, Pedro Veliça, Laura Barbieri, Craig E. Wheelock, Peppi Koivunen, James A. Nathan, Iosifina P. Foskolou, Randall S. Johnson

Bibliographic record

VenueNature Metabolism · 2023
Typearticle
Languageen
FieldImmunology and Microbiology
TopicImmune cells in cancer
Canadian institutionsnot available
FundersFundação para a Ciência e a TecnologiaEvelyn TrustLister Institute of Preventive MedicineKnut och Alice Wallenbergs StiftelseKarolinska InstitutetDirectorate for Biological SciencesQueen's UniversityBarncancerfondenCancerfondenWellcome TrustVetenskapsrådetGovernment of CanadaCanadian Institutes of Health ResearchWellcome
KeywordsCatabolismMetabolismChemistryBiochemistryEnzymeCellProtein subunitCell metabolismAmino acidT cellFunction (biology)Metabolic intermediateCell biologyBiologyImmune systemGene

Abstract

fetched live from OpenAlex

Abstract T cell function and fate can be influenced by several metabolites: in some cases, acting through enzymatic inhibition of α-ketoglutarate-dependent dioxygenases, in others, through post-translational modification of lysines in important targets. We show here that glutarate, a product of amino acid catabolism, has the capacity to do both, and has potent effects on T cell function and differentiation. We found that glutarate exerts those effects both through α-ketoglutarate-dependent dioxygenase inhibition, and through direct regulation of T cell metabolism via glutarylation of the pyruvate dehydrogenase E2 subunit. Administration of diethyl glutarate, a cell-permeable form of glutarate, alters CD8 + T cell differentiation and increases cytotoxicity against target cells. In vivo administration of the compound is correlated with increased levels of both peripheral and intratumoural cytotoxic CD8 + T cells. These results demonstrate that glutarate is an important regulator of T cell metabolism and differentiation with a potential role in the improvement of T cell immunotherapy.

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 score0.001
Threshold uncertainty score0.003

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)0.0010.000

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 head0.237
Teacher spread0.231 · 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

Citations55
Published2023
Admission routes1
Has abstractyes

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Same venueNature MetabolismSame topicImmune cells in cancerFrench-language works237,207