MétaCan
Menu
Back to cohort
Record W3010473572 · doi:10.1172/jci130426

IRF4 instructs effector Treg differentiation and immune suppression in human cancer

2020· article· en· W3010473572 on OpenAlexfundno aff
Giorgia Alvisi, Jolanda Brummelman, Simone Puccio, Emilia Maria Cristina Mazza, Elisa Paoluzzi Tomada, Agnese Losurdo, Veronica Zanon, Clelia Peano, Federico Colombo, Alice Scarpa, Marco Alloisio, Ajithkumar Vasanthakumar, Rahul Roychoudhuri, Marinos Kallikourdis, Massimiliano Pagani, Egesta Lopci, Pierluigi Novellis, Jonas Blume, Axel Kallies, Giulia Veronesi, Enrico Lugli

Bibliographic record

VenueJournal of Clinical Investigation · 2020
Typearticle
Languageen
FieldImmunology and Microbiology
TopicImmune Cell Function and Interaction
Canadian institutionsnot available
FundersNational Health and Medical Research CouncilMedical Research CouncilBristol-Myers Squibb CanadaAssociazione Italiana per la Ricerca sul CancroFondazione Umberto VeronesiUniversity of MelbourneBiotechnology and Biological Sciences Research CouncilMinistero della SaluteBristol-Myers SquibbDeutsche ForschungsgemeinschaftCancer Research UK
KeywordsIRF4BiologyEffectorCancer researchImmunosuppressionImmune systemImmunologyTranscription factorTumor microenvironmentGeneGenetics

Abstract

fetched live from OpenAlex

The molecular mechanisms responsible for the high immunosuppressive capacity of CD4+ Tregs in tumors are not well known. High-dimensional single-cell profiling of T cells from chemotherapy-naive individuals with non-small-cell lung cancer identified the transcription factor IRF4 as specifically expressed by a subset of intratumoral CD4+ effector Tregs with superior suppressive activity. In contrast to the IRF4- counterparts, IRF4+ Tregs expressed a vast array of suppressive molecules, and their presence correlated with multiple exhausted subpopulations of T cells. Integration of transcriptomic and epigenomic data revealed that IRF4, either alone or in combination with its partner BATF, directly controlled a molecular program responsible for immunosuppression in tumors. Accordingly, deletion of Irf4 exclusively in Tregs resulted in delayed tumor growth in mice while the abundance of IRF4+ Tregs correlated with poor prognosis in patients with multiple human cancers. Thus, a common mechanism underlies immunosuppression in the tumor microenvironment irrespective of the tumor type.

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 head0.056
GPT teacher head0.347
Teacher spread0.291 · 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

Citations203
Published2020
Admission routes1
Has abstractyes

Explore more

Same venueJournal of Clinical InvestigationSame topicImmune Cell Function and InteractionFrench-language works237,207