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Record W4361217347 · doi:10.1101/2023.03.27.533229

Inducing an oxidized redox-balance improves anti-tumor CD8 <sup>+</sup> T cell function

2023· preprint· en· W4361217347 on OpenAlexafffund
Ju Hee Oh, Rachel A. Cederberg, Erin Tanaka, Luisa Bopp, Terri Ser, Sara Niyyati, Annette E. Patterson, Neeku Amanat, Jared Dutra, Patricia Ye, Meredith R. Clark, Kirsten A. Ward‐Hartstonge, Anne‐Sophie Archambault, Janice Tsui, Philipp F. Lange, Sue Tsai, C. Bruce Verchere, Yongjin Park, Mario Fabri, Kevin L. Bennewith, Ramon I. Klein Geltink

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2023
Typepreprint
Languageen
FieldImmunology and Microbiology
TopicImmune Cell Function and Interaction
Canadian institutionsUniversity of AlbertaBC Children's HospitalSpinal Cord Injury BCUniversity of British Columbia
FundersNatural Sciences and Engineering Research Council of CanadaCanadian Institutes of Health ResearchUniversität zu KölnUniversity of British ColumbiaBC Children's HospitalMichael Smith Health Research BCDeutsche ForschungsgemeinschaftChildren's Hospital Foundation
KeywordsCytotoxic T cellImmunotherapyIn vivoCD8Cell biologyT cellCancer immunotherapyTumor microenvironmentEx vivoCancer researchEffectorChemistryIn vitroCytokineBiologyImmune systemImmunologyBiochemistry

Abstract

fetched live from OpenAlex

SUMMARY Cancer immunotherapy using antigen-specific CD8 + T cells depends on long-lasting anti-tumor function of the in vitro expanded T cells. T cell function is intricately linked to the activity of many metabolic pathways directly impacting the ability of CD8 + T cells to kill tumor cells. Metabolic conditioning in vitro better prepares CD8 + T cells for in vivo survival, tumor infiltration and tumor clearance. The mechanism underlying in vitro metabolic conditioning-induced augmented in vivo T cell function remains poorly understood. Here we show that metabolic conditioning of CD8 + effector T cells induces an oxidized cellular redox balance at least in part mediated by increased mitochondrial reactive oxygen species (ROS). This redox shift contributes to enhanced in vivo persistence and tumor clearance. In human tumour-infiltrating T cells, altering the redox balance ex-vivo reinvigorated pro-inflammatory cytokine production. Therefore, we believe that redox alterations present a targetable pathway to increase T cell-based anti-tumor immunotherapy efficacy.

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 score0.003
Threshold uncertainty score0.011

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)0.0030.000

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 head0.014
GPT teacher head0.214
Teacher spread0.200 · 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

Citations1
Published2023
Admission routes2
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)→Same topicImmune Cell Function and Interaction→French-language works237,207→