ArticleJournal of immunology (Baltimore, Md. : 1950)2014
Histone deacetylase inhibitor sensitizes apoptosis-resistant melanomas to cytotoxic human T lymphocytes through regulation of TRAIL/DR5 pathway.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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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.
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.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Review
- Advances in the study of death receptor 5.Frontiers in pharmacology · 2025Review
- Review
- The paradigm of drug resistance in cancer: an epigenetic perspective.Bioscience reports · 2022Review
- Enhancing the Effect of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Signaling and Arginine Deprivation in Melanoma.International journal of molecular sciences · 2021Review
- FKBP51 Affects TNF-Related Apoptosis Inducing Ligand Response in Melanoma.Frontiers in cell and developmental biology · 2021Article
- Association of Valproic Acid Use, a Potent Histone Deacetylase Inhibitor, and Melanoma Risk.The Journal of investigative dermatology · 2020Article
- Understanding the Mechanisms by Which Epigenetic Modifiers Avert Therapy Resistance in Cancer.Frontiers in oncology · 2020Review
- Novel Apoptosis-Inducing Agents for the Treatment of Cancer, a New Arsenal in the Toolbox.Cancers · 2019Review
- Review
- How patients with an intact immune system develop head and neck cancer.Oral oncology · 2019Review
- Disulfide bond-disrupting agents activate the tumor necrosis family-related apoptosis-inducing ligand/death receptor 5 pathway.Cell death discovery · 2019Article
- Modulation of antitumor immunity with histone deacetylase inhibitors.Immunotherapy · 2017Review
- Review
- Article
- Autophagic Mechanism in Anti-Cancer Immunity: Its Pros and Cons for Cancer Therapy.International journal of molecular sciences · 2017Review
- HDACs and HDAC Inhibitors in Cancer Development and Therapy.Cold Spring Harbor perspectives in medicine · 2016Review
- Regulation of TRAIL-receptor expression by the ubiquitin-proteasome system.International journal of molecular sciences · 2014Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Modern immune therapies (PD-1/PD-L1 and CTLA-4 checkpoints blockade and adoptive cell transfer) have remarkably improved the response rates of metastatic melanoma. These modalities rely on the killing potential of CTL as proximal mediator of antimelanoma responses. Mechanisms of tumor resistance to and the predominant cytotoxic pathway(s) used by melanoma-reactive CTL are important outcome determinants. We hypothesized that downmodulation of death receptors (DRs) in addition to aberrant apoptotic signaling might confer resistance to death signals delivered by CTL. To test these two hypotheses, we used an in vitro model of MART CTL-resistant melanoma sublines. TCR-transgenic and patient-derived CTLs used the TRAIL cytotoxic pathway through DR5. Furthermore, recombinant human TRAIL and drozitumab (anti-DR5 agonistic mAb) were used to explicitly verify the contribution of the DR5/TRAIL pathway in killing melanomas. CTL resistance was due to DR5 downregulation and an inverted ratio of pro- to antiapoptotic molecules, both of which were reversed by the histone deacetylase inhibitor suberoylanilide hydroxanic acid. Apoptosis negative (c-IAP-2 and Bcl-xL) and positive (DR5) regulators were potential incriminators partly regulating CTL sensitivity. These preclinical findings suggest that exposure to this chromatin remodeling drug of immune-resistant melanomas can skew toward an intracellular proapoptotic milieu, increase DR expression, and overcome acquired immune resistance.
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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.