{"doi":"10.1016/j.immuni.2024.01.011","title":"Signaling via a CD27-TRAF2-SHP-1 axis during naive T cell activation promotes memory-associated gene regulatory networks","abstract":"T (Tn) cells with homotrimeric CD70 on antigen-presenting cells (APCs) is necessary for T cell memory fate determination. Here, we examined CD27 signaling during Tn cell activation and differentiation. In conjunction with T cell receptor (TCR) stimulation, ligation of CD27 by a synthetic trimeric CD70 ligand triggered CD27 internalization and degradation, suggesting active regulation of this signaling axis. Internalized CD27 recruited the signaling adaptor TRAF2 and the phosphatase SHP-1, thereby modulating TCR and CD28 signals. CD27-mediated modulation of TCR signals promoted transcription factor circuits that induced memory rather than effector associated gene programs, which are induced by CD28 costimulation. CD27-costimulated chimeric antigen receptor (CAR)-engineered T cells exhibited improved tumor control compared with CD28-costimulated CAR-T cells. Thus, CD27 signaling during Tn cell activation promotes memory properties with relevance to T cell immunotherapy.","journal":"Immunity","year":2024,"id":419200,"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":42,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9547,"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":468249,"name":"Yun Lo","orcid":"0000-0001-8145-3674","position":1,"is_corresponding":false},{"id":1209188,"name":"Elena Fulton","orcid":null,"position":2,"is_corresponding":false},{"id":634404,"name":"Olivia G. 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Kluesner","orcid":"0000-0001-5828-9204","position":18,"is_corresponding":false},{"id":109702,"name":"Valentin Voillet","orcid":"0000-0002-5751-3881","position":19,"is_corresponding":false},{"id":232695,"name":"Vishaka Muhunthan","orcid":"0000-0003-4733-9602","position":20,"is_corresponding":false},{"id":708402,"name":"Fionnuala Morrish","orcid":null,"position":21,"is_corresponding":false},{"id":30180,"name":"James M. Olson","orcid":"0000-0001-5990-6534","position":22,"is_corresponding":false},{"id":18054,"name":"Raphaël Gottardo","orcid":"0000-0002-3867-0232","position":23,"is_corresponding":false},{"id":267024,"name":"Jay F. Sarthy","orcid":"0000-0001-5244-7865","position":24,"is_corresponding":false},{"id":45084,"name":"Steven Henikoff","orcid":"0000-0002-7621-8685","position":25,"is_corresponding":false},{"id":295732,"name":"Lucas B. Sullivan","orcid":"0000-0002-6745-8222","position":26,"is_corresponding":false},{"id":94709,"name":"Scott N. 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