{"doi":"10.1158/2159-8290.cd-20-1677","title":"Integrative Bulk and Single-Cell Profiling of Premanufacture T-cell Populations Reveals Factors Mediating Long-Term Persistence of CAR T-cell Therapy","abstract":"Abstract The adoptive transfer of chimeric antigen receptor (CAR) T cells represents a breakthrough in clinical oncology, yet both between- and within-patient differences in autologously derived T cells are a major contributor to therapy failure. To interrogate the molecular determinants of clinical CAR T-cell persistence, we extensively characterized the premanufacture T cells of 71 patients with B-cell malignancies on trial to receive anti-CD19 CAR T-cell therapy. We performed RNA-sequencing analysis on sorted T-cell subsets from all 71 patients, followed by paired Cellular Indexing of Transcriptomes and Epitopes (CITE) sequencing and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) on T cells from six of these patients. We found that chronic IFN signaling regulated by IRF7 was associated with poor CAR T-cell persistence across T-cell subsets, and that the TCF7 regulon not only associates with the favorable naïve T-cell state, but is maintained in effector T cells among patients with long-term CAR T-cell persistence. These findings provide key insights into the underlying molecular determinants of clinical CAR T-cell function. Significance: To improve clinical outcomes for CAR T-cell therapy, there is a need to understand the molecular determinants of CAR T-cell persistence. These data represent the largest clinically annotated molecular atlas in CAR T-cell therapy to date, and significantly advance our understanding of the mechanisms underlying therapeutic efficacy. This article is highlighted in the In This Issue feature, p. 2113","journal":"Cancer Discovery","year":2021,"id":146614,"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":207,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9484,"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":225138,"name":"Changya Chen","orcid":"0000-0003-4421-2462","position":1,"is_corresponding":false},{"id":623302,"name":"Rajat K. Das","orcid":"0000-0001-6807-6093","position":2,"is_corresponding":false},{"id":503532,"name":"Peng Gao","orcid":"0000-0002-7785-2389","position":3,"is_corresponding":false},{"id":225139,"name":"Chia‐Hui Chen","orcid":"0000-0001-9927-6215","position":4,"is_corresponding":false},{"id":623303,"name":"Shovik Bandyopadhyay","orcid":"0000-0003-3919-3914","position":5,"is_corresponding":false},{"id":496141,"name":"Yangyang Ding","orcid":"0000-0003-1588-2571","position":6,"is_corresponding":false},{"id":342898,"name":"Yasin Uzun","orcid":"0000-0003-3478-3499","position":7,"is_corresponding":false},{"id":342897,"name":"Wenbao Yu","orcid":"0000-0001-8860-2644","position":8,"is_corresponding":false},{"id":296321,"name":"Qin Zhu","orcid":"0000-0001-5539-6071","position":9,"is_corresponding":false},{"id":623304,"name":"Regina M. Myers","orcid":"0000-0002-2542-2061","position":10,"is_corresponding":false},{"id":496143,"name":"Stephan A. Grupp","orcid":"0000-0001-8030-7595","position":11,"is_corresponding":false},{"id":496142,"name":"David M. Barrett","orcid":"0000-0002-8302-3114","position":12,"is_corresponding":false},{"id":225110,"name":"Kai Tan","orcid":"0000-0002-9104-5567","position":13,"is_corresponding":false},{"id":496140,"name":"Gregory M. Chen","orcid":"0000-0002-4083-5083","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-18T23:42:24.567796Z","pmid":"33820778","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}