ArticleFrontiers in immunology2020
Scaffolding LSD1 Inhibitors Impair NK Cell Metabolism and Cytotoxic Function Through Depletion of Glutathione.
Article in Frontiers in immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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.
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.
Who cites it
20 citing papers in PubMed, 35 citations in OpenAlex.
- The dual roles of lysine-specific demethylase 1 (KDM1A/LSD1) in the modulation of tumor immune microenvironment and its inhibitors in colorectal cancer.Journal of molecular medicine (Berlin, Germany) · 2026Review
- LSD1 ablation promotes mammary tumor metastasis by attenuating NK cell-mediated anti-tumor immunity.bioRxiv : the preprint server for biology · 2026Article
- Epigenetic Regulation of Immune Responses in Endocrine-Related Cancers and Its Role in Immunotherapy.Cancers · 2025Review
- The epigenetic hallmarks of immune cells in cancer.Molecular cancer · 2025Review
- Role of lysine-specific demethylase 1 in immunotherapy of gastric cancer: An update.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024Article
- Current and future therapeutic strategies for high-grade gliomas leveraging the interplay between epigenetic regulators and kinase signaling networks.Journal of experimental & clinical cancer research : CR · 2024Review
- Review
- LSD1: an emerging face in altering the tumor microenvironment and enhancing immune checkpoint therapy.Journal of biomedical science · 2023Review
- Histone demethylases in the regulation of immunity and inflammation.Cell death discovery · 2023Review
- Viscosalactone B, a natural LSD1 inhibitor, inhibits proliferation in vitro and in vivo against prostate cancer cells.Investigational new drugs · 2023Article
- Targeting LSD1 in tumor immunotherapy: rationale, challenges and potential.Frontiers in immunology · 2023Review
- Comparison of pharmacological inhibitors of lysine-specific demethylase 1 in glioblastoma stem cells reveals inhibitor-specific efficacy profiles.Frontiers in neurology · 2023Article
- LSD1 inhibitors for cancer treatment: Focus on multi-target agents and compounds in clinical trials.Frontiers in pharmacology · 2023Review
- Epigenetic modulation and prostate cancer: Paving the way for NK cell anti-tumor immunity.Frontiers in immunology · 2023Review
- Epigenetic regulation of natural killer cell memory.Immunological reviews · 2022Review
- Lysine specific demethylase 1 is a molecular driver and therapeutic target in sarcoma.Frontiers in oncology · 2022Review
- Review
- ComprehensiveACS pharmacology & translational science · 2021Article
- Roles of lysine-specific demethylase 1 (LSD1) in homeostasis and diseases.Journal of biomedical science · 2021Review
- Epigenetic Regulation of NK Cell-Mediated Antitumor Immunity.Frontiers in immunology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Cell therapies such as chimeric-antigen receptor (CAR) T-cells and NK cells are cutting-edge methods for treating cancer and other diseases. There is high interest in optimizing drug treatment regimens to best work together with emerging cell therapies, such as targeting epigenetic enzymes to stimulate recognition of tumor cells by immune cells. Herein, we uncover new mechanisms of the histone demethylase LSD1, and various inhibitors targeting unique domains of LSD1, in the function of NK cells grown for cell therapy. Catalytic inhibitors (tranylcypromine and the structural derivatives GSK LSD1 and RN-1) can irreversibly block the demethylase activity of LSD1, while scaffolding inhibitors (SP-2509 and clinical successor SP-2577, also known as seclidemstat) disrupt epigenetic complexes that include LSD1. Relevant combinations of LSD1 inhibitors with cell therapy infusions and immune checkpoint blockade have shown efficacy in pre-clinical solid tumor models, reinforcing a need to understand how these drugs would impact T- and NK cells. We find that scaffolding LSD1 inhibitors potently reduce oxidative phosphorylation and glycolysis of NK cells, and higher doses induce mitochondrial reactive oxygen species and depletion of the antioxidant glutathione. These effects are unique to scaffolding inhibitors compared to catalytic, to NK cells compared to T-cells, and importantly, can fully ablate the lytic capacity of NK cells. Supplementation with biologically achievable levels of glutathione rescues NK cell cytolytic function but not NK cell metabolism. Our results suggest glutathione supplementation may reverse NK cell activity suppression in patients treated with seclidemstat.
Indexed as
Identifiers
What OpenQuestion holds
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.