{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T11:13:01Z","timestamp":1788952381392,"version":"build-2803163510"},"reference-count":47,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Kathy Goh Professorship","award":["09\/FY2024\/DP(SL)\/76-A163"],"award-info":[{"award-number":["09\/FY2024\/DP(SL)\/76-A163"]}]},{"name":"Breast Diseases Research Fund","award":["09\/FY2024\/EX\/34-A86"],"award-info":[{"award-number":["09\/FY2024\/EX\/34-A86"]}]},{"name":"National Research Medical Council Singapore Young Individual Research Grant","award":["MOH-000232"],"award-info":[{"award-number":["MOH-000232"]}]},{"name":"Khoo Postdoctoral Fellowship Award","award":["Duke-NUS-KPFA\/2019\/0034"],"award-info":[{"award-number":["Duke-NUS-KPFA\/2019\/0034"]}]},{"name":"Singapore Therapeutics Development Review Pre-Pilot","award":["H23G1a0009"],"award-info":[{"award-number":["H23G1a0009"]}]},{"name":"SingHealth Duke-NUS Genomic Medicine Centre Seed Grant","award":["SDDC\/FY2023\/EX\/79-A117"],"award-info":[{"award-number":["SDDC\/FY2023\/EX\/79-A117"]}]},{"name":"Moe Tier 1","award":["FY2024-MOET1-0002"],"award-info":[{"award-number":["FY2024-MOET1-0002"]}]},{"name":"National Medical Research Council Open Fund\u2014Individual Research Grant","award":["MOH-001890-00"],"award-info":[{"award-number":["MOH-001890-00"]}]},{"name":"National Medical Research Council Open Fund\u2014Individual Research Grant","award":["MOH-000144"],"award-info":[{"award-number":["MOH-000144"]}]},{"name":"National Medical Research Council Singapore Translational Research Investigator Award","award":["MOH-000248-00"],"award-info":[{"award-number":["MOH-000248-00"]}]},{"name":"National Medical Research Council Singapore Translational Research Investigator Award","award":["MOH-001827-00"],"award-info":[{"award-number":["MOH-001827-00"]}]},{"name":"3rd A*STAR-AMed Joint Grant","award":["R23I2IR070"],"award-info":[{"award-number":["R23I2IR070"]}]},{"name":"Tan Yew Oo Professorship","award":["09\/FY2023\/DP(SL)\/142-A197(a)"],"award-info":[{"award-number":["09\/FY2023\/DP(SL)\/142-A197(a)"]}]},{"name":"Verdant Foundation"},{"name":"NCC Cancer Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Triple-negative breast cancer (TNBC) exhibits aggressive biology and heterogeneous immune infiltration. Lysine-specific demethylase 1 (LSD1\/KDM1A) is an epigenetic regulator implicated in oncogenic transcriptional programs, but its role in immune exclusion remains incompletely defined. Methods: LSD1 expression was evaluated by immunohistochemistry in TNBC specimens and correlated with survival. Functional effects of LSD1 depletion or pharmacological inhibition were assessed in TNBC cell lines and patient-derived xenograft organoids (PDXOs). Transcriptomic, ChIP-seq, multiplex immunofluorescence, and GeoMX digital spatial profiling analyses were integrated to characterize LSD1-associated transcriptional, chromatin, and immune programs. PBMC-PDXO co-cultures evaluated the effects of LSD1 inhibition on tumor growth and immune cell infiltration. Results: High LSD1 expression was associated with inferior overall survival, hypoxia-associated programs and suppressed immune pathways. LSD1-high tumors exhibited reduced infiltration of T cells, B cells, NKT-like cells, and macrophages. Spatial profiling revealed suppressed innate immune responses and type I interferon signaling within B-cell and T-cell compartments, respectively. ChIP-seq demonstrated preferential LSD1 occupancy at AP-1 motif-enriched regions, while co-immunoprecipitation supported association with AP-1 complexes. Integration of LSD1 chromatin occupancy sites with transcriptomics data identified SPPL2A and NCOA3 as candidate LSD1-regulated genes associated with interferon-\u03b3 response pathways. LSD1 depletion increased SPPL2A, NCOA3, MHC-I and PD-L1 expression. LSD1 inhibition reduced PDXO growth and increased immune cell infiltration. Conclusions: LSD1 is associated with a poor clinical outcome and immune exclusion in TNBC. These findings support a role for LSD1 in AP-1-associated chromatin regulation and interferon-\u03b3-related transcriptional response; they warrant further investigation into LSD1 inhibition as a therapeutic strategy for immune-cold TNBCs.<\/jats:p>","DOI":"10.3390\/cancers18182920","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T10:19:16Z","timestamp":1788949156000},"page":"2920","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["LSD1 Promotes Immune Exclusion and Suppresses IFN-\u03b3-Associated Transcriptional Programs in Triple-Negative Breast Cancer"],"prefix":"10.3390","volume":"18","author":[{"given":"Dong Yeul","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Anatomical Pathology, Singapore General Hospital, Singapore 169856, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2173-9192","authenticated-orcid":false,"given":"Jing Han","family":"Hong","sequence":"additional","affiliation":[{"name":"Cancer and Stem Cell Biology Programme, Duke-NUS Graduate Medical School, Singapore 169857, 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Singapore"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2709-1972","authenticated-orcid":false,"given":"Bernett","family":"Lee","sequence":"additional","affiliation":[{"name":"Centre of Biomedical Informatics, Nanyang Technological University, Singapore 636921, 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Singapore"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Hui Xin","family":"Lau","sequence":"additional","affiliation":[{"name":"Department of Anatomical Pathology, Singapore General Hospital, Singapore 169856, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Joe Poh Sheng","family":"Yeong","sequence":"additional","affiliation":[{"name":"Department of Anatomical Pathology, Singapore General Hospital, Singapore 169856, Singapore"},{"name":"Institute of Molecular and Cell Biology, 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Medicine, National University of Singapore, Singapore 117597, Singapore"},{"name":"Center for Computational Biology, Duke-NUS Graduate Medical School, Singapore 169857, Singapore"},{"name":"Bioinformatics Institute, Agency of Science, Technology and Research (A*STAR), Singapore 138634, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Bin Tean","family":"Teh","sequence":"additional","affiliation":[{"name":"Cancer and Stem Cell Biology Programme, Duke-NUS Graduate Medical School, Singapore 169857, Singapore"},{"name":"National Cancer Centre Singapore, Singapore 168583, 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