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.
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.
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Who cites it
11 citing papers in PubMed, 15 citations in OpenAlex.
- 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 · 2026Review
- HDAC inhibitors reverse YAP-driven immune resistance in NSCLC: mechanistic and translational evidence.Journal for immunotherapy of cancer · 2026Article
- Commensal microbe-derived butyrate enhances T follicular helper cell function to boost mucosal vaccine efficacy.Microbiome · 2026Article
- Post-Translational Modifications in Cancer-Associated CD8⁺ T-Cell Exhaustion: Mechanisms and Therapeutic Opportunities.International journal of biological sciences · 2026Review
- Enhancing immunotherapy efficacy in multiple myeloma and chronic lymphocytic leukemia: from combinatorial therapeutic approaches to gut microbiota modulation.Frontiers in immunology · 2026Review
- TMB as a predictive biomarker for ICI response in TNBC: current evidence and future directions for augmented anti-tumor responses.Clinical and experimental medicine · 2025Review
- Miniaturized scalable arrayed CRISPR screening in primary cells enables discovery at the single donor resolution.Scientific reports · 2025Article
- Hdac1 as an early determinant of intermediate-exhausted CD8Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Advances of HDAC inhibitors in tumor therapy: potential applications through immune modulation.Frontiers in oncology · 2025Review
- Epigenetic and metabolic reprogramming via nanotechnology: a synergistic approach to cancer vaccination in lung tumors.Frontiers in genetics · 2025Review
- Epigenetic regulation of the tumor microenvironment: A leading force driving pancreatic cancer.Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] · 2024Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
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.
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Registered trials
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.