{"doi":"10.1126/sciimmunol.adn1945","title":"Stem-like memory and precursors of exhausted T cells share a common progenitor defined by ID3 expression","abstract":"Stem-like T cells are attractive immunotherapeutic targets in patients with cancer given their ability to proliferate and differentiate into effector progeny. Thus, identifying T cells with enhanced stemness and understanding their developmental requirements are of broad clinical and therapeutic interest. Here, we demonstrate that during acute infection, the transcriptional regulator inhibitor of DNA binding 3 (ID3) identifies stem-like T cells that are uniquely adapted to generate precursors of exhausted T (Tpex) cells in response to chronic infection or cancer. Expression of ID3 itself enables Tpex cells to sustain T cell responses in chronic infection or cancer, whereas loss of ID3 results in impaired maintenance of CD8 T cell immunity. Furthermore, we demonstrate that interleukin-1 (IL-1) family members, including IL-36β and IL-18, promote the generation of ID3 + T cells that mediate superior tumor control. Overall, we identify ID3 as a common denominator of stem-like T cells in both acute and chronic infections that is specifically required to sustain T cell responses to chronic stimulation.","journal":"Science Immunology","year":2025,"id":509321,"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":37,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9658,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1363239,"name":"Amania A. 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Mackay","orcid":"0000-0002-8496-6632","position":20,"is_corresponding":false},{"id":1363250,"name":"Ajithkumar Vasanthakumar","orcid":"0000-0002-1620-7781","position":21,"is_corresponding":false},{"id":846015,"name":"David Bending","orcid":"0000-0003-0071-1163","position":22,"is_corresponding":false},{"id":36696,"name":"Wei Shi","orcid":"0000-0003-1182-7735","position":23,"is_corresponding":false},{"id":302507,"name":"Weiguo Cui","orcid":"0000-0003-1562-9218","position":24,"is_corresponding":false},{"id":345401,"name":"Jan Schröder","orcid":"0000-0001-5270-0605","position":25,"is_corresponding":false},{"id":567466,"name":"Ricky W. Johnstone","orcid":"0000-0001-7053-9237","position":26,"is_corresponding":false},{"id":656806,"name":"Axel Kallies","orcid":"0000-0002-6312-6968","position":27,"is_corresponding":false},{"id":656804,"name":"Daniel T. 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