{"doi":"10.21203/rs.3.rs-87705/v1","title":"Ablation of Histone Demethylase KDM5B in Melanoma Augments Anti-Tumor Immunity through Upregulation of Retroelements","abstract":"Abstract Epigenetic therapies are emerging strategies to prime host immune system to immunotherapies. Here we show that depletion of H3K4 demethylase KDM5B in melanoma cells induces anti-tumor T cell immunity through up-regulation of retroelements, which activates cytosolic nucleic acid sensing pathways and subsequent type I interferon responses. Mechanistically, KDM5B recruits H3K9 methyltransferase SETDB1 to the chromatin to repress these retroelements. Ablation of KDM5B enhances responses of poorly immunogenic melanoma tumors to anti PD-1 treatment. Our studies suggest that therapies targeting KDM5B are a novel approach to enhance tumor immunogenicity and overcome immunotherapy resistance.","journal":"Research Square","year":2020,"id":132213,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9566,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":110478,"name":"Wesley L. Cai","orcid":"0000-0002-3871-5509","position":1,"is_corresponding":false},{"id":587272,"name":"Xiaoni Liu","orcid":"0000-0002-8547-3290","position":2,"is_corresponding":false},{"id":587273,"name":"Durga Thakral","orcid":"0000-0001-5420-3354","position":3,"is_corresponding":false},{"id":368803,"name":"Goran Micevic","orcid":"0000-0003-0329-1053","position":4,"is_corresponding":false},{"id":374037,"name":"Carmen J. Booth","orcid":"0000-0002-2153-738X","position":5,"is_corresponding":false},{"id":245496,"name":"Kim Blenman","orcid":"0000-0001-6070-0728","position":6,"is_corresponding":false},{"id":226315,"name":"Lucia B. Jilaveanu","orcid":"0000-0001-8900-5083","position":7,"is_corresponding":false},{"id":231012,"name":"William Damsky","orcid":"0000-0003-0975-4071","position":8,"is_corresponding":false},{"id":231013,"name":"Meaghan K. McGeary","orcid":"0000-0002-8505-7158","position":9,"is_corresponding":false},{"id":68933,"name":"Mario Sznol","orcid":"0000-0002-4359-8749","position":10,"is_corresponding":false},{"id":226323,"name":"Harriet M. Kluger","orcid":"0000-0002-4932-9873","position":11,"is_corresponding":false},{"id":105840,"name":"Akiko Iwasaki","orcid":"0000-0002-7824-9856","position":12,"is_corresponding":false},{"id":13279,"name":"Marcus Bosenberg","orcid":"0000-0003-0166-1612","position":13,"is_corresponding":false},{"id":110497,"name":"Qin Yan","orcid":"0000-0003-4077-453X","position":14,"is_corresponding":false},{"id":330394,"name":"Shang‐Min Zhang","orcid":null,"position":0,"is_corresponding":true}],"reference_count":30,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:16:07.542484Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}