{"doi":"10.1101/2020.03.13.989558","title":"Genome-wide Screens Identify Lineage- and Tumor Specific-Genes Modulating MHC-I and MHC-II Immunosurveillance in Human Lymphomas","abstract":"Summary Tumors frequently subvert MHC class I (MHC-I) peptide presentation to evade CD8+ T cell immunosurveillance. To better define the regulatory networks controlling antigen presentation, we employed genome-wide screening in human diffuse large B cell lymphomas (DLBCLs). This approach revealed dozens of novel genes that positively and negatively modulate MHC-I cell surface levels. Identified genes cluster in multiple pathways including cytokine signaling, mRNA processing, endosomal trafficking, and protein metabolism. Many genes exhibit lymphoma subtype- or tumor-specific MHC-I regulation, and a majority of primary DLBCL tumors display genetic alterations in multiple regulators. We establish that the HSP90 co-chaperone SUGT1 is a major positive regulator of both MHC-I and MHC-II cell surface expression. Further, pharmacological inhibition of two negative regulators of antigen presentation, EZH2 and thymidylate synthase, enhances DLBCL MHC-I presentation. These and other genes represent potential targets for manipulating MHC-I immunosurveillance in cancers, infectious diseases, and autoimmunity.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":124720,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9495,"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":106819,"name":"James D. Phelan","orcid":"0000-0001-8950-2485","position":1,"is_corresponding":false},{"id":261941,"name":"Megan E. Gumina","orcid":"0000-0003-2590-9547","position":2,"is_corresponding":false},{"id":261942,"name":"Boya Wang","orcid":"0000-0002-4201-8474","position":3,"is_corresponding":false},{"id":261943,"name":"Jesse H. Arbuckle","orcid":"0000-0003-3652-3543","position":4,"is_corresponding":false},{"id":261944,"name":"Jaroslav Hollý","orcid":"0000-0002-0589-9655","position":5,"is_corresponding":false},{"id":255929,"name":"Rigel J. Kishton","orcid":"0000-0002-5682-3896","position":6,"is_corresponding":false},{"id":264931,"name":"Tovah E. Markowitz","orcid":null,"position":7,"is_corresponding":false},{"id":264932,"name":"Mina O. Seedhom","orcid":null,"position":8,"is_corresponding":false},{"id":264933,"name":"Nathan Fridlyand","orcid":null,"position":9,"is_corresponding":false},{"id":106818,"name":"George W. Wright","orcid":"0000-0003-0003-0843","position":10,"is_corresponding":false},{"id":96765,"name":"Da Wei Huang","orcid":"0000-0002-6793-9966","position":11,"is_corresponding":false},{"id":261945,"name":"Michele Ceribelli","orcid":"0000-0001-9857-9521","position":12,"is_corresponding":false},{"id":258191,"name":"Craig J. Thomas","orcid":"0000-0001-9386-9001","position":13,"is_corresponding":false},{"id":261946,"name":"Justin Lack","orcid":"0000-0003-0584-4010","position":14,"is_corresponding":false},{"id":257262,"name":"Nicholas P. Restifo","orcid":null,"position":15,"is_corresponding":false},{"id":261947,"name":"Thomas M. Kristie","orcid":"0000-0003-3647-3339","position":16,"is_corresponding":false},{"id":35688,"name":"Louis M. Staudt","orcid":"0000-0002-1735-2892","position":17,"is_corresponding":false},{"id":17894,"name":"Jonathan W. Yewdell","orcid":"0000-0002-3826-1906","position":18,"is_corresponding":false},{"id":261940,"name":"Devin Dersh","orcid":"0000-0002-3763-4192","position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":null,"created_at":"2026-07-18T23:15:11.632153Z","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":[]}