{"doi":"10.1016/j.celrep.2021.109992","title":"Mapping the evolution of T cell states during response and resistance to adoptive cellular therapy","abstract":"To elucidate mechanisms by which T cells eliminate leukemia, we study donor lymphocyte infusion (DLI), an established immunotherapy for relapsed leukemia. We model T cell dynamics by integrating longitudinal, multimodal data from 94,517 bone marrow-derived single T cell transcriptomes in addition to chromatin accessibility and single T cell receptor sequencing from patients undergoing DLI. We find that responsive tumors are defined by enrichment of late-differentiated T cells before DLI and rapid, durable expansion of early differentiated T cells after treatment, highly similar to \"terminal\" and \"precursor\" exhausted subsets, respectively. Resistance, in contrast, is defined by heterogeneous T cell dysfunction. Surprisingly, early differentiated T cells in responders mainly originate from pre-existing and novel clonotypes recruited to the leukemic microenvironment, rather than the infusion. Our work provides a paradigm for analyzing longitudinal single-cell profiling of scenarios beyond adoptive cell therapy and introduces Symphony, a Bayesian approach to infer regulatory circuitry underlying T cell subsets, with broad relevance to exhaustion antagonists across cancers.","journal":"Cell Reports","year":2021,"id":155405,"datarank":1.5550723841769512,"base_score":4.0943445622221,"endowment":4.0943445622221,"self_citation_contribution":0.6141516843333151,"citation_network_contribution":0.940920699843636,"self_endowment_contribution":0.6141516843333151,"citer_contribution":0.940920699843636,"corpus_percentile":null,"corpus_rank":null,"citation_count":59,"citer_count":38,"citers_with_citation_signal":33,"citers_with_endowment":33,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.94,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":559371,"name":"Elham Azizi","orcid":"0000-0001-5059-6971","position":1,"is_corresponding":false},{"id":559372,"name":"Cassandra Burdziak","orcid":"0000-0001-6008-7783","position":2,"is_corresponding":false},{"id":396151,"name":"Vinhkhang N. 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