Evidence map›Paper›PMID 38169329›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2024

Histone Deacetylase Inhibitors Directly Modulate T Cell Gene Expression and Signaling and Promote Development of Effector-Exhausted T Cells in Murine Tumors.

Mohammed L Ibrahim, Hong Zheng, Margaret L Barlow, Yousuf Latif, Zhihua Chen, Xiaoqing Yu, Amer A Beg

Open access · greenAbstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
3.5field-weighted citation impact, top 7% of its field
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

11 citing papers in PubMed, 15 citations in OpenAlex.

  1. Epigenetic insights and innovations for overcoming barriers in CAR-T cell therapy for cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  2. Article
  3. Article
  4. Review
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  7. Article
  8. Hdac1 as an early determinant of intermediate-exhausted CD8Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  9. Review
  10. Review
  11. Epigenetic regulation of the tumor microenvironment: A leading force driving pancreatic cancer.Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] · 2024
    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

7 authors at 2 institutions in 2 countries.

Mohammed L IbrahimDepartment of Immunology, Moffitt Cancer Center, Tampa, FL.ORCID 0000-0002-1686-0561
Hong ZhengDepartment of Immunology, Moffitt Cancer Center, Tampa, FL.
Margaret L BarlowDepartment of Immunology, Moffitt Cancer Center, Tampa, FL.ORCID 0009-0007-6737-1024
Yousuf LatifDepartment of Immunology, Moffitt Cancer Center, Tampa, FL.ORCID 0009-0003-8252-881X
Zhihua ChenDepartment of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, FL.ORCID 0000-0002-9127-0510
Xiaoqing YuDepartment of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, FL.
Amer A BegDepartment of Immunology, Moffitt Cancer Center, Tampa, FL.
Moffitt Cancer Center · USCairo University · EG

Funding

TRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI Christine O'Connell · 1998 to 2026
$93.5M
Augmenting T cell trafficking and functionality through novel combinations of epigenetic agents and PD-1 blockadeR01CA212169 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI BEG, AMER AZIZ · 2017 to 2021
$2.0M
NCI NIH HHS P30 CA076292NCI NIH HHS R01 CA212169
6 · The paper itself

Abstract

Epigenetic regulation plays a crucial role in the development and progression of cancer, including the regulation of antitumor immunity. The reversible nature of epigenetic modifications offers potential therapeutic avenues for cancer treatment. In particular, histone deacetylase (HDAC) inhibitors (HDACis) have been shown to promote antitumor T cell immunity by regulating myeloid cell types, enhancing tumor Ag presentation, and increasing expression of chemokines. HDACis are currently being evaluated to determine whether they can increase the response rate of immune checkpoint inhibitors in cancer patients. Although the potential direct effect of HDACis on T cells likely impacts antitumor immunity, little is known about how HDAC inhibition alters the transcriptomic profile of T cells. In this article, we show that two clinical-stage HDACis profoundly impact gene expression and signaling networks in CD8+ and CD4+ T cells. Specifically, HDACis promoted T cell effector function by enhancing expression of TNF-α and IFN-γ and increasing CD8+ T cell cytotoxicity. Consistently, in a murine tumor model, HDACis led to enrichment of CD8+ T cell subsets with high expression of effector molecules (Prf1, Ifng, Gzmk, and Grmb) but also molecules associated with T cell exhaustion (Tox, Pdcd1, Lag3, and Havcr2). HDACis further generated a tumor microenvironment dominated by myeloid cells with immune suppressive signatures. These results indicate that HDACis directly and favorably augment T cell effector function but also increase their exhaustion signal in the tumor microenvironment, which may add a layer of complexity for achieving clinical benefit in combination with immune checkpoint inhibitors.

Indexed as

Histone Deacetylase InhibitorsNeoplasmsAnimalsCD8-Positive T-LymphocytesEpigenesis, GeneticGene ExpressionHumansImmune Checkpoint InhibitorsMiceTumor MicroenvironmentHistone Deacetylase InhibitorsImmune Checkpoint Inhibitors

Identifiers

PMID38169329
PMCPMC10872871
OpenAlexW4390536491

What OpenQuestion holds

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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.