{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:57:05Z","timestamp":1791860225810,"version":"4.3.4"},"reference-count":74,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"6620","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2022,11,11]]},"abstract":"<jats:p>\n                    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\n                    <jats:italic>MED12<\/jats:italic>\n                    and\n                    <jats:italic>CCNC<\/jats:italic>\n                    , components of the Mediator kinase module. Targeted\n                    <jats:italic>MED12<\/jats:italic>\n                    deletion enhanced antitumor activity and sustained the effector phenotype in CAR- and T cell receptor\u2013engineered T cells, and inhibition of CDK8\/19 kinase activity increased expansion of nonengineered T cells.\n                    <jats:italic>MED12<\/jats:italic>\n                    -deficient T cells manifested increased core Meditator chromatin occupancy at transcriptionally active enhancers\u2014most notably for STAT and AP-1 transcription factors\u2014and increased\n                    <jats:italic>IL2RA<\/jats:italic>\n                    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.\n                  <\/jats:p>","DOI":"10.1126\/science.abn5647","type":"journal-article","created":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T13:58:42Z","timestamp":1668088722000},"source":"Crossref","is-referenced-by-count":159,"title":["Enhanced T cell effector activity by targeting the Mediator kinase module"],"prefix":"10.1126","volume":"378","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9480-7320","authenticated-orcid":true,"given":"Katherine A.","family":"Freitas","sequence":"first","affiliation":[{"name":"Immunology Graduate Program, Stanford University School of Medicine, Stanford, CA, USA."},{"name":"Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, 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