{"doi":"10.1038/s41375-024-02303-w","title":"CREB1 promotes expression of immune checkpoint HLA-E leading to immune escape in multiple myeloma","abstract":"Multiple myeloma (MM) cells effectively escape anti-tumoral immunity to survive in the tumor microenvironment (TME). Herein, we identify non-classical major histocompatibility complex (MHC) class I molecule HLA-E as a major contributing factor in immune escape. Clinically, HLA-E expression correlates with aggressive disease features such as t(4;14) and CD56 expression and is induced by IFN-gamma (IFN-γ) in the TME. We discovered that HLA-E is regulated by cAMP responsive element binding protein 1 (CREB1) transcription factor by direct promoter binding; genomic and pharmacological inhibition of CREB1 reduced HLA-E levels even in the presence of IFN-γ or IFN-γ activating agents, such as immunomodulatory drugs and panobinostat. HLA-E binds to natural killer group 2A (NKG2A), delivering an inhibitor signal to natural killer (NK) cells. Treatment with a CREB1 inhibitor was able to restore NK cell-mediated cytotoxicity against MM cell lines and patient samples. In conclusion, our results strongly demonstrate that CREB1 inhibition promotes anti-tumoral immunity in MM by limiting HLA-E expression and enhancing the activity of NK cells.","journal":"Leukemia","year":2024,"id":427378,"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":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9525,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1228082,"name":"Allen J. Robinette","orcid":null,"position":1,"is_corresponding":false},{"id":1228083,"name":"Laila Huric","orcid":null,"position":2,"is_corresponding":false},{"id":1228084,"name":"Jamie Schuetz","orcid":null,"position":3,"is_corresponding":false},{"id":1228085,"name":"Kameron Dona","orcid":null,"position":4,"is_corresponding":false},{"id":967872,"name":"Don Benson","orcid":null,"position":5,"is_corresponding":false},{"id":65246,"name":"Emanuele Cocucci","orcid":"0000-0002-0088-9845","position":6,"is_corresponding":false},{"id":728519,"name":"Francesca Cottini","orcid":"0000-0001-8676-7840","position":7,"is_corresponding":false},{"id":1227550,"name":"Aya Ismael","orcid":"0009-0003-5635-1061","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-19T01:58:47.805440Z","pmid":"38902472","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":[]}