{"title":"Epigenetic programming via lysine-specific demethylase 1 regulates responses to immune checkpoint blockade.","authors":"Xiaoshuang Niu, Bin Yu","doi":"10.1016/j.tips.2026.09.006","DOIUrl":null,"url":null,"abstract":"<p><p>Immune checkpoint blockade has revolutionized cancer therapy, but durable benefit remains limited by immune-cold tumor states, poor antigen presentation, T cell exhaustion, and adaptive resistance. Recent studies position lysine-specific demethylase 1 (LSD1) as a druggable epigenetic regulator that links these barriers across tumor and immune cells. Emerging evidence shows that targeting LSD1 can restore major histocompatibility complex class I antigen presentation, activate viral mimicry and interferon programs, modulate programmed death-ligand 1 in a context-dependent manner, influence CD8<sup>+</sup> T cell state transitions, and restrain tumor plasticity. In this review, we feature these mechanistic advances, compare evolving drug classes, and outline biomarker-guided strategies that may support the rational development of next-generation combination immunotherapy.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":24.0000,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Trends in pharmacological sciences","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.tips.2026.09.006","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Immune checkpoint blockade has revolutionized cancer therapy, but durable benefit remains limited by immune-cold tumor states, poor antigen presentation, T cell exhaustion, and adaptive resistance. Recent studies position lysine-specific demethylase 1 (LSD1) as a druggable epigenetic regulator that links these barriers across tumor and immune cells. Emerging evidence shows that targeting LSD1 can restore major histocompatibility complex class I antigen presentation, activate viral mimicry and interferon programs, modulate programmed death-ligand 1 in a context-dependent manner, influence CD8+ T cell state transitions, and restrain tumor plasticity. In this review, we feature these mechanistic advances, compare evolving drug classes, and outline biomarker-guided strategies that may support the rational development of next-generation combination immunotherapy.
期刊介绍：
Trends in Pharmacological Sciences (TIPS) is a monthly peer-reviewed reviews journal that focuses on a wide range of topics in pharmacology, pharmacy, pharmaceutics, and toxicology. Launched in 1979, TIPS publishes concise articles discussing the latest advancements in pharmacology and therapeutics research.
The journal encourages submissions that align with its core themes while also being open to articles on the biopharma regulatory landscape, science policy and regulation, and bioethics.
Each issue of TIPS provides a platform for experts to share their insights and perspectives on the most exciting developments in the field. Through rigorous peer review, the journal ensures the quality and reliability of published articles.
Authors are invited to contribute articles that contribute to the understanding of pharmacology and its applications in various domains. Whether it's exploring innovative drug therapies or discussing the ethical considerations of pharmaceutical research, TIPS provides a valuable resource for researchers, practitioners, and policymakers in the pharmacological sciences.
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