ArticleJournal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer2022
Targeting Lysine-Specific Demethylase 1 Rescues Major Histocompatibility Complex Class I Antigen Presentation and Overcomes Programmed Death-Ligand 1 Blockade Resistance in SCLC.
Article in Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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The trial behind it
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Who cites it
91 citing papers in PubMed, 120 citations in OpenAlex.
- NOTCH1 reverses immune suppression in small cell lung cancer through reactivation of STING.The Journal of clinical investigation · 2025Trial
- Molecular classification and biomarkers of outcome with immunotherapy in extensive-stage small-cell lung cancer: analyses of the CASPIAN phase 3 study.Molecular cancer · 2024Trial
- Clinical Benefit From Immunotherapy in Patients With SCLC Is Associated With Tumor Capacity for Antigen Presentation.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2023Trial
- Reframing cancer therapy through tumor plasticity.Nature cancer · 2026Review
- LSD1 Promotes Immune Exclusion and Suppresses IFN-γ-Associated Transcriptional Programs in Triple-Negative Breast Cancer.Cancers · 2026Article
- Review
- Survival trends in extensive-stage small cell lung cancer in the pre-immunotherapy and immunotherapy eras: a population-based SEER study.Journal of thoracic disease · 2026Article
- [Expert Consensus on Immunotherapy for Extensive-stage Small Cell Lung Cancer Based on Molecular Subtyping].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Review
- Cancer stem cell plasticity: mechanisms, immune microenvironment crosstalk, and therapeutic implications.Journal of hematology & oncology · 2026Review
- Mechanisms of resistance in small cell lung cancer.Chinese medical journal · 2026Review
- Review
- A tunable Cas12a platform for single-cell perturbation screening and CRISPRi.Nature communications · 2026Article
- Research progress on immune microenvironment and biomarkers of small cell lung cancer.Journal of thoracic disease · 2026Review
- TAF1 Suppresses MHC-I Expression and Correlates with Poor Immunotherapy Response in Small Cell Lung Cancer.Biomedicines · 2026Article
- Article
- UHRF1 drives subtype-independent aggressiveness and immune evasion in small cell lung cancer through PRC2 interactions.iScience · 2026Article
- LSD1 inhibitor, TAS1440, disrupts INSM1-LSD1 complex activating tumor-suppressive pathways via transcriptional reprogramming in neuroendocrine SCLC.Nature communications · 2026Article
- Subtype-specific dependencies and therapeutic opportunities in small cell lung cancer.Science advances · 2026Review
- Small Cell Lung Cancer Classification: Unraveling Heterogeneity to Enable Personalized Treatments.Cancer research · 2026Review
- Eukaryote initiation factor 6 modulates small-cell lung carcinoma plasticity via the integrin-FAK signaling axis.Nature communications · 2026Article
31 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors at 1 institution in 1 country.
Funding
Abstract
introductionSCLC is a highly aggressive neuroendocrine tumor that is characterized by early acquired therapeutic resistance and modest benefit from immune checkpoint blockade (ICB). Repression of the major histocompatibility complex class I (MHC-I) represents a key mechanism driving resistance to T cell-based immunotherapies.
methodsWe evaluated the role of the lysine-specific demethylase 1 (LSD1) as a determinant of MHC-I expression, functional antigen presentation, and immune activation in SCLC in vitro and in vivo through evaluation of both human SCLC cell lines and immunocompetent mouse models.
resultsWe found that targeted inhibition of LSD1 in SCLC restores MHC-I cell surface expression and transcriptionally activates genes encoding the antigen presentation pathway. LSD1 inhibition further activates interferon signaling, induces tumor-intrinsic immunogenicity, and sensitizes SCLC cells to MHC-I-restricted T cell cytolysis. Combination of LSD1 inhibitor with ICB augments the antitumor immune response in refractory SCLC models. Together, these data define a role for LSD1 as a potent regulator of MHC-I antigen presentation and provide rationale for combinatory use of LSD1 inhibitors with ICB to improve therapeutic response in SCLC.
conclusionsEpigenetic silencing of MHC-I in SCLC contributes to its poor response to ICB. Our study identifies a previously uncharacterized role for LSD1 as a regulator of MHC-I antigen presentation in SCLC. LSD1 inhibition enables MHC-I-restricted T cell cytolysis, induces immune activation, and augments the antitumor immune response to ICB in SCLC.
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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.