{"doi":"10.1172/jci179703","title":"An epigenetic pathway regulates MHC-II expression and function in B cell lymphoma models","abstract":"Mutations or homozygous deletions of MHC class II (MHC-II) genes are commonly found in B cell lymphomas that develop in immune-privileged sites and have been associated with patient survival. However, the mechanisms regulating MHC-II expression, particularly through genetic and epigenetic factors, are not yet fully understood. In this study, we identified a key signaling pathway involving the histone H2AK119 deubiquitinase BRCA1 associated protein 1 (BAP1), the interferon regulatory factor interferon regulatory factor 1 (IRF1), and the MHC-II transactivator class II transactivator (CIITA), which directly activates MHC-II gene expression. Disruption of the BAP1/IRF1/CIITA axis leads to a functional attenuation of MHC-II expression and MHC-II-dependent immune cell infiltration, leading to accelerated tumor growth in immunocompetent mice. Additionally, we demonstrated that pharmacological inhibition of polycomb repressive complex 1 (PRC1) - which deposits histone H2K119Ub and opposes BAP1 activity - can restore MHC-II gene expression in BAP1-deficient B cell lymphoma cells. These findings suggest that BAP1 may function as a tumor suppressor by regulating the tumor microenvironment and immune response. Our study also establishes the rationale for therapeutic strategies to restore tumor-specific MHC-II expression and enhance immunotherapy outcomes at epigenetic levels in B cell lymphoma treatment.","journal":"Journal of Clinical Investigation","year":2025,"id":516871,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9501,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1224732,"name":"Oguzhan Beytullahoglu","orcid":null,"position":1,"is_corresponding":false},{"id":1383239,"name":"Rima Tulaiha","orcid":null,"position":2,"is_corresponding":false},{"id":1383240,"name":"Amanda Luvisotto","orcid":null,"position":3,"is_corresponding":false},{"id":346286,"name":"Aileen Patricia Szczepanski","orcid":null,"position":4,"is_corresponding":false},{"id":711663,"name":"Natsumi Tsuboyama","orcid":"0000-0002-8620-3479","position":5,"is_corresponding":false},{"id":344355,"name":"Zibo Zhao","orcid":"0000-0003-1089-2375","position":6,"is_corresponding":false},{"id":586791,"name":"Lu Wang","orcid":"0000-0002-3134-2519","position":7,"is_corresponding":false},{"id":1224174,"name":"Te Zhang","orcid":"0000-0002-8383-4531","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":null,"created_at":"2026-07-19T02:48:54.768083Z","pmid":"39817454","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":[]}