{"doi":"10.1084/jem.20240797","title":"Suppression of melanoma by mice lacking MHC-II: Mechanisms and implications for cancer immunotherapy","abstract":"Immune checkpoint inhibitors interfere with T cell exhaustion but often fail to cure or control cancer long-term in patients. Using a genetic screen in C57BL/6J mice, we discovered a mutation in host H2-Aa that caused strong immune-mediated resistance to mouse melanomas. H2-Aa encodes an MHC class II α chain, and its absence in C57BL/6J mice eliminates all MHC-II expression. H2-Aa deficiency, specifically in dendritic cells (DC), led to a quantitative increase in type 2 conventional DC (cDC2) and a decrease in cDC1. H2-Aa-deficient cDC2, but not cDC1, were essential for melanoma suppression and effectively cross-primed and recruited CD8 T cells into tumors. Lack of T regulatory cells, also observed in H2-Aa deficiency, contributed to melanoma suppression. Acute disruption of H2-Aa was therapeutic in melanoma-bearing mice, particularly when combined with checkpoint inhibition, which had no therapeutic effect by itself. Our findings suggest that inhibiting MHC-II may be an effective immunotherapeutic approach to enhance immune responses to cancer.","journal":"The Journal of Experimental Medicine","year":2024,"id":443546,"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":0.9492,"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":368857,"name":"Dawson Medler","orcid":"0000-0001-7282-3805","position":1,"is_corresponding":false},{"id":368856,"name":"Jianhui Wang","orcid":"0000-0002-6335-8355","position":2,"is_corresponding":false},{"id":1258157,"name":"Rachel Browning","orcid":"0009-0008-2364-311X","position":3,"is_corresponding":false},{"id":395801,"name":"Aijie Liu","orcid":"0000-0002-4777-7795","position":4,"is_corresponding":false},{"id":585467,"name":"Sara Schneider","orcid":"0000-0002-6277-1578","position":5,"is_corresponding":false},{"id":1258769,"name":"Claudia Duran Bojorquez","orcid":null,"position":6,"is_corresponding":false},{"id":297436,"name":"Ashwani Kumar","orcid":"0000-0002-6374-0976","position":7,"is_corresponding":false},{"id":364915,"name":"Xiaohong Li","orcid":"0000-0001-8357-5587","position":8,"is_corresponding":false},{"id":576804,"name":"Jiexia Quan","orcid":"0000-0002-4762-3833","position":9,"is_corresponding":false},{"id":364914,"name":"Sara Ludwig","orcid":"0000-0001-5752-6730","position":10,"is_corresponding":false},{"id":298836,"name":"James J. Moresco","orcid":"0000-0003-1178-1642","position":11,"is_corresponding":false},{"id":240348,"name":"Chao Xing","orcid":"0000-0002-1838-0502","position":12,"is_corresponding":false},{"id":364918,"name":"Eva Marie Y. Moresco","orcid":"0000-0002-2049-7291","position":13,"is_corresponding":false},{"id":51949,"name":"Bruce Beutler","orcid":"0000-0002-3639-246X","position":14,"is_corresponding":false},{"id":576803,"name":"Hexin Shi","orcid":"0000-0001-8075-511X","position":0,"is_corresponding":true}],"reference_count":75,"raw_metadata":null,"created_at":"2026-07-19T02:01:29.001453Z","pmid":"39470607","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":[]}