{"doi":"10.1136/jitc-2022-005852","title":"BRCA1 deficiency in mature CD8<sup>+</sup> T lymphocytes impairs antitumor immunity","abstract":"Women with BRCA1 germline mutations have approximately an 80% lifetime chance of developing breast cancer. While the tumor suppressor function of BRCA1 in breast epithelium has been studied extensively, it is not clear whether BRCA1 deficiency in non-breast somatic cells also contribute to tumorigenesis. Here, we report that mouse Brca1 knockout (KO) in mature T lymphocytes compromises host antitumor immune response to transplanted syngeneic mouse mammary tumors. T cell adoptive transfer further corroborates CD8 + T cell-intrinsic impact of Brca1 KO on antitumor adaptive immunity. T cell-specific Brca1 KO mice exhibit fewer total CD8 + , more exhausted, reduced cytotoxic, and reduced memory tumor-infiltrating T cell populations. Consistent with the preclinical data, cancer-free BRCA1 mutation-carrying women display lower abundance of circulating CD8 + lymphocytes than the age-matched control group. Thus, our findings support the notion that BRCA1 deficiency in adaptive immunity could contribute to BRCA1 -related tumorigenesis. We also suggest that prophylactic boosting of adaptive immunity may reduce cancer incidence among at-risk women.","journal":"Journal for ImmunoTherapy of Cancer","year":2023,"id":340637,"datarank":0.41588830833596724,"base_score":2.772588722239781,"endowment":2.772588722239781,"self_citation_contribution":0.41588830833596724,"citation_network_contribution":0.0,"self_endowment_contribution":0.41588830833596724,"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":0.9517,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":766248,"name":"Leilei Qi","orcid":null,"position":1,"is_corresponding":false},{"id":341851,"name":"Huai-Chin Chiang","orcid":"0000-0002-7616-3362","position":2,"is_corresponding":false},{"id":144101,"name":"Haihui Pan","orcid":null,"position":3,"is_corresponding":false},{"id":617652,"name":"Xiaowen Zhang","orcid":"0000-0002-0072-2439","position":4,"is_corresponding":false},{"id":1075668,"name":"Alexandra Z. Greenbaum","orcid":"0000-0002-7162-8036","position":5,"is_corresponding":false},{"id":1075669,"name":"Elizabeth Stark","orcid":"0009-0002-6337-5021","position":6,"is_corresponding":false},{"id":640936,"name":"Li‐Ju Wang","orcid":"0000-0003-2745-2819","position":7,"is_corresponding":false},{"id":238480,"name":"Yidong Chen","orcid":"0000-0001-6806-2185","position":8,"is_corresponding":false},{"id":1076215,"name":"Bassem R. Haddad","orcid":null,"position":9,"is_corresponding":false},{"id":1076216,"name":"Dionyssia Clagett","orcid":null,"position":10,"is_corresponding":false},{"id":242394,"name":"Claudine Isaacs","orcid":"0000-0002-9646-1260","position":11,"is_corresponding":false},{"id":433068,"name":"Richard Elledge","orcid":null,"position":12,"is_corresponding":false},{"id":367503,"name":"Anélia Horvath","orcid":"0000-0003-4117-013X","position":13,"is_corresponding":false},{"id":341854,"name":"Yanfen Hu","orcid":"0000-0001-9595-1631","position":14,"is_corresponding":false},{"id":237974,"name":"Rong Li","orcid":"0009-0008-6177-2246","position":15,"is_corresponding":false},{"id":341850,"name":"Bogang Wu","orcid":"0000-0003-1654-198X","position":0,"is_corresponding":true}],"reference_count":25,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:10:58.548803Z","pmid":"36731891","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":[]}