Evidence map›Paper›PMID 39486420›Full record

ArticleCell reports. Medicine2024

Degradation of IKZF1 prevents epigenetic progression of T cell exhaustion in an antigen-specific assay.

Tristan Tay, Gayathri Bommakanti, Elizabeth Jaensch, Aparna Gorthi, Iswarya Karapa Reddy, Yan Hu, Ruochi Zhang, Aatman S Doshi, Sin Lih Tan, Verena Brucklacher-Waldert and 6 more

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In one paragraph

Article in Cell reports. Medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
–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

15 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Review
  8. Review
  9. Article
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  12. Review
  13. From concept to cure: The evolution of CAR-T cell therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  14. Article
  15. Terminally exhausted CD8Frontiers in immunology · 2025
    Review
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

16 authors.

Tristan TayDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA; Gene Regulation Observatory, Broad Institute, Cambridge, MA, USA.
Gayathri BommakantiOncology R&D, AstraZeneca, Waltham, MA, USA.
Elizabeth JaenschOncology R&D, AstraZeneca, Waltham, MA, USA.
Aparna GorthiOncology R&D, AstraZeneca, Waltham, MA, USA.
Iswarya Karapa ReddyOncology R&D, AstraZeneca, Waltham, MA, USA.
Yan HuDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA; Gene Regulation Observatory, Broad Institute, Cambridge, MA, USA.
Ruochi ZhangDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA; Gene Regulation Observatory, Broad Institute, Cambridge, MA, USA.
Aatman S DoshiOncology R&D, AstraZeneca, Waltham, MA, USA.
Sin Lih TanRevvity, Cambridge, UK.
Verena Brucklacher-WaldertRevvity, Cambridge, UK.
Laura PrickettOncology R&D, AstraZeneca, Waltham, MA, USA.
James KurasawaOncology R&D, AstraZeneca, Gaithersburg, MD, USA.
Michael Glen OverstreetOncology R&D, AstraZeneca, Gaithersburg, MD, USA.
Steven CriscioneOncology R&D, AstraZeneca, Waltham, MA, USA.
Jason Daniel BuenrostroDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA; Gene Regulation Observatory, Broad Institute, Cambridge, MA, USA. Electronic address: jason_buenrostro@harvard.edu.
Deanna A MeleOncology R&D, AstraZeneca, Waltham, MA, USA. Electronic address: deanna.mele@astrazeneca.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In cancer, chronic antigen stimulation drives effector T cells to exhaustion, limiting the efficacy of T cell therapies. Recent studies have demonstrated that epigenetic rewiring governs the transition of T cells from effector to exhausted states and makes a subset of exhausted T cells non-responsive to PD1 checkpoint blockade. Here, we describe an antigen-specific assay for T cell exhaustion that generates T cells phenotypically and transcriptionally similar to those found in human tumors. We perform a screen of human epigenetic regulators, identifying IKZF1 as a driver of T cell exhaustion. We determine that the IKZF1 degrader iberdomide prevents exhaustion by blocking chromatin remodeling at T cell effector enhancers and preserving the binding of AP-1, NF-κB, and NFAT. Thus, our study uncovers a role for IKZF1 as a driver of T cell exhaustion through epigenetic modulation, providing a rationale for the use of iberdomide in solid tumors to prevent T cell exhaustion.

Indexed as

Epigenesis, GeneticIkaros Transcription FactorT-LymphocytesChromatin Assembly and DisassemblyHumansNeoplasmsNFATC Transcription FactorsNF-kappa BT-Cell ExhaustionTranscription Factor AP-1Ikaros Transcription FactorIKZF1 protein, humanNFATC Transcription FactorsNF-kappa BTranscription Factor AP-1

Identifiers

PMID39486420
PMCPMC11604474

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.