{"doi":"10.1126/science.abn5647","title":"Enhanced T cell effector activity by targeting the Mediator kinase module","abstract":"T cells are the major arm of the immune system responsible for controlling and regressing cancers. To identify genes limiting T cell function, we conducted genome-wide CRISPR knockout screens in human chimeric antigen receptor (CAR) T cells. Top hits were MED12 and CCNC , components of the Mediator kinase module. Targeted MED12 deletion enhanced antitumor activity and sustained the effector phenotype in CAR- and T cell receptor–engineered T cells, and inhibition of CDK8/19 kinase activity increased expansion of nonengineered T cells. MED12 -deficient T cells manifested increased core Meditator chromatin occupancy at transcriptionally active enhancers—most notably for STAT and AP-1 transcription factors—and increased IL2RA expression and interleukin-2 sensitivity. These results implicate Mediator in T cell effector programming and identify the kinase module as a target for enhancing potency of antitumor T cell responses.","journal":"Science","year":2022,"id":233072,"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":147,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9487,"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":262617,"name":"Julia A. Belk","orcid":"0000-0003-4724-6158","position":1,"is_corresponding":false},{"id":225336,"name":"Elena Sotillo","orcid":"0000-0002-3993-1932","position":2,"is_corresponding":false},{"id":845643,"name":"Patrick J. Quinn","orcid":"0000-0002-4406-727X","position":3,"is_corresponding":false},{"id":845644,"name":"María C. Ramello","orcid":"0000-0001-8108-141X","position":4,"is_corresponding":false},{"id":555320,"name":"Meena Malipatlolla","orcid":null,"position":5,"is_corresponding":false},{"id":237496,"name":"Bence Dániel","orcid":"0000-0002-2410-8767","position":6,"is_corresponding":false},{"id":21650,"name":"Katalin Sandor","orcid":"0000-0003-2892-4865","position":7,"is_corresponding":false},{"id":615457,"name":"Dorota D. Klysz","orcid":"0000-0002-6733-6110","position":8,"is_corresponding":false},{"id":845645,"name":"Jeremy Bjelajac","orcid":"0000-0001-7628-1652","position":9,"is_corresponding":false},{"id":457182,"name":"Peng Xu","orcid":"0000-0002-7573-4813","position":10,"is_corresponding":false},{"id":266172,"name":"Kylie Burdsall","orcid":"0000-0001-7089-2532","position":11,"is_corresponding":false},{"id":845646,"name":"Victor Tieu","orcid":"0000-0003-0135-9587","position":12,"is_corresponding":false},{"id":845647,"name":"Vandon T. Duong","orcid":"0000-0002-8103-3757","position":13,"is_corresponding":false},{"id":845648,"name":"Micah G. Donovan","orcid":"0000-0002-3463-2570","position":14,"is_corresponding":false},{"id":225341,"name":"Evan W. Weber","orcid":"0000-0001-5039-2899","position":15,"is_corresponding":false},{"id":26,"name":"Howard Y. Chang","orcid":"0000-0002-9459-4393","position":16,"is_corresponding":false},{"id":225335,"name":"Robbie G. Majzner","orcid":"0000-0001-6969-8011","position":17,"is_corresponding":false},{"id":313603,"name":"Joaquı́n M. Espinosa","orcid":"0000-0001-9048-1941","position":18,"is_corresponding":false},{"id":21653,"name":"Ansuman T. Satpathy","orcid":"0000-0002-5167-537X","position":19,"is_corresponding":false},{"id":225351,"name":"Crystal L. Mackall","orcid":"0000-0003-0359-9023","position":20,"is_corresponding":false},{"id":640061,"name":"Katherine A. Freitas","orcid":"0000-0001-9480-7320","position":0,"is_corresponding":true}],"reference_count":74,"raw_metadata":null,"created_at":"2026-07-19T00:21:25.223756Z","pmid":"36356142","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":[]}