{"doi":"10.1084/jem.20212169","title":"Tumor-induced double positive T cells display distinct lineage commitment mechanisms and functions","abstract":"Transcription factors ThPOK and Runx3 regulate the differentiation of \"helper\" CD4+ and \"cytotoxic\" CD8+ T cell lineages respectively, inducing single positive (SP) T cells that enter the periphery with the expression of either the CD4 or CD8 co-receptor. Despite the expectation that these cell fates are mutually exclusive and that mature CD4+CD8+ double positive (DP) T cells are present in healthy individuals and augmented in the context of disease, yet their molecular features and pathophysiologic role are disputed. Here, we show DP T cells in murine and human tumors as a heterogenous population originating from SP T cells which re-express the opposite co-receptor and acquire features of the opposite cell type's phenotype and function following TCR stimulation. We identified distinct clonally expanded DP T cells in human melanoma and lung cancer by scRNA sequencing and demonstrated their tumor reactivity in cytotoxicity assays. Our findings indicate that antigen stimulation induces SP T cells to differentiate into DP T cell subsets gaining in polyfunctional characteristics.","journal":"The Journal of Experimental Medicine","year":2022,"id":239497,"datarank":1.3088385105471911,"base_score":3.912023005428146,"endowment":3.912023005428146,"self_citation_contribution":0.586803450814222,"citation_network_contribution":0.7220350597329691,"self_endowment_contribution":0.586803450814222,"citer_contribution":0.7220350597329691,"corpus_percentile":null,"corpus_rank":null,"citation_count":49,"citer_count":47,"citers_with_citation_signal":31,"citers_with_endowment":31,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9491,"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":297331,"name":"Andrew Chow","orcid":"0000-0003-1151-2450","position":1,"is_corresponding":false},{"id":227532,"name":"Levi Mangarin","orcid":"0000-0003-1219-6998","position":2,"is_corresponding":false},{"id":345821,"name":"Heng Pan","orcid":"0000-0002-5407-5687","position":3,"is_corresponding":false},{"id":490805,"name":"Jiajia Zhang","orcid":"0000-0003-4623-6134","position":4,"is_corresponding":false},{"id":288782,"name":"Nicholas Ceglia","orcid":"0000-0001-9387-103X","position":5,"is_corresponding":false},{"id":615676,"name":"Justina X. 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Chaft","orcid":"0000-0002-5838-9982","position":15,"is_corresponding":false},{"id":254632,"name":"Patrick M. Forde","orcid":"0000-0001-6925-6344","position":16,"is_corresponding":false},{"id":311788,"name":"Justin F. Gainor","orcid":"0000-0001-8697-4081","position":17,"is_corresponding":false},{"id":90691,"name":"Matthew D. Hellmann","orcid":"0000-0002-2670-9777","position":18,"is_corresponding":false},{"id":106424,"name":"Vinod P. Balachandran","orcid":"0000-0002-2956-223X","position":19,"is_corresponding":false},{"id":22198,"name":"Sohrab P. Shah","orcid":"0000-0001-6402-523X","position":20,"is_corresponding":false},{"id":62880,"name":"Kellie N. Smith","orcid":"0000-0002-6295-8930","position":21,"is_corresponding":false},{"id":59439,"name":"Drew M. Pardoll","orcid":"0000-0001-6215-1013","position":22,"is_corresponding":false},{"id":41043,"name":"Olivier Elemento","orcid":"0000-0002-8061-9617","position":23,"is_corresponding":false},{"id":3666,"name":"Jedd D. 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