{"doi":"10.1016/j.celrep.2022.111153","title":"Cancer genes disfavoring T cell immunity identified via integrated systems approach","abstract":"Adoptive T cell therapies (ACT) have been curative for a limited number of cancer patients. The sensitization of cancer cells to T cell killing may expand the benefit of these therapies for more patients. To this end, we use a three-step approach to identify cancer genes that disfavor T cell immunity. First, we profile gene transcripts upregulated by cancer under selection pressure from T cell killing. Second, we identify potential tumor gene targets and pathways that disfavor T cell killing using signaling pathway activation libraries and genome-wide loss-of-function CRISPR-Cas9 screens. Finally, we implement pharmacological perturbation screens to validate these targets and identify BIRC2, ITGAV, DNPEP, BCL2, and ERRα as potential ACT-drug combination candidates. Here, we establish that BIRC2 limits antigen presentation and T cell recognition of tumor cells by suppressing IRF1 activity and provide evidence that BIRC2 inhibition in combination with ACT is an effective strategy to increase efficacy.","journal":"Cell Reports","year":2022,"id":269730,"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":0.9575,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":255934,"name":"Shashank J. Patel","orcid":"0000-0001-6973-6997","position":1,"is_corresponding":false},{"id":290241,"name":"Amy E. Decker","orcid":null,"position":2,"is_corresponding":false},{"id":255930,"name":"Suman K. Vodnala","orcid":"0000-0001-6753-5788","position":3,"is_corresponding":false},{"id":562958,"name":"Maggie Cam","orcid":"0000-0001-8190-9766","position":4,"is_corresponding":false},{"id":235387,"name":"Tori N. Yamamoto","orcid":"0000-0003-1965-7822","position":5,"is_corresponding":false},{"id":555933,"name":"Yogin Patel","orcid":"0000-0002-1951-009X","position":6,"is_corresponding":false},{"id":255933,"name":"Madhusudhanan Sukumar","orcid":"0000-0003-2293-4448","position":7,"is_corresponding":false},{"id":226273,"name":"Zhiya Yu","orcid":"0000-0003-3742-5902","position":8,"is_corresponding":false},{"id":933406,"name":"Michelle Ji","orcid":null,"position":9,"is_corresponding":false},{"id":255927,"name":"Amanda N. Henning","orcid":"0000-0002-0935-9963","position":10,"is_corresponding":false},{"id":226272,"name":"Devikala Gurusamy","orcid":"0000-0002-1727-8653","position":11,"is_corresponding":false},{"id":255932,"name":"Douglas C. Palmer","orcid":"0000-0001-5018-5734","position":12,"is_corresponding":false},{"id":933407,"name":"Roxana A. Stefanescu","orcid":null,"position":13,"is_corresponding":false},{"id":225302,"name":"Andrew T. Girvin","orcid":"0000-0002-2031-9209","position":14,"is_corresponding":false},{"id":932958,"name":"Winifred Lo","orcid":"0009-0009-6943-6164","position":15,"is_corresponding":false},{"id":498013,"name":"Anna Pasetto","orcid":"0000-0002-5254-2173","position":16,"is_corresponding":false},{"id":268734,"name":"Parisa Malekzadeh","orcid":"0000-0002-1749-1198","position":17,"is_corresponding":false},{"id":268739,"name":"Drew C. Deniger","orcid":"0000-0002-9299-9688","position":18,"is_corresponding":false},{"id":288305,"name":"Kris C. Wood","orcid":"0000-0002-5887-2253","position":19,"is_corresponding":false},{"id":32220,"name":"Neville E. Sanjana","orcid":"0000-0002-1504-0027","position":20,"is_corresponding":false},{"id":257262,"name":"Nicholas P. Restifo","orcid":null,"position":21,"is_corresponding":false},{"id":255929,"name":"Rigel J. Kishton","orcid":"0000-0002-5682-3896","position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":null,"created_at":"2026-07-19T00:27:22.602796Z","pmid":"35926468","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":[]}