{"doi":"10.1126/sciimmunol.adg1094","title":"TIM-3 <sup>+</sup> CD8 T cells with a terminally exhausted phenotype retain functional capacity in hematological malignancies","abstract":"Chronic antigen stimulation is thought to generate dysfunctional CD8 T cells. Here, we identify a CD8 T cell subset in the bone marrow tumor microenvironment that, despite an apparent terminally exhausted phenotype (T PHEX ), expressed granzymes, perforin, and IFN-γ. Concurrent gene expression and DNA accessibility revealed that genes encoding these functional proteins correlated with BATF expression and motif accessibility. IFN-γ + T PHEX effectively killed myeloma with comparable efficacy to transitory effectors, and disease progression correlated with numerical deficits in IFN-γ + T PHEX . We also observed IFN-γ + T PHEX within CD19-targeted chimeric antigen receptor T cells, which killed CD19 + leukemia cells. An IFN-γ + T PHEX gene signature was recapitulated in T EX cells from human cancers, including myeloma and lymphoma. Here, we characterize a T EX subset in hematological malignancies that paradoxically retains function and is distinct from dysfunctional T EX found in chronic viral infections. Thus, IFN-γ + T PHEX represent a potential target for immunotherapy of blood cancers.","journal":"Science Immunology","year":2024,"id":418468,"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":50,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9598,"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":634404,"name":"Olivia G. Waltner","orcid":"0000-0001-7021-0431","position":1,"is_corresponding":false},{"id":242725,"name":"Ping Zhang","orcid":"0000-0002-0311-6725","position":2,"is_corresponding":false},{"id":759395,"name":"Shuichiro Takahashi","orcid":"0000-0002-3850-0559","position":3,"is_corresponding":false},{"id":886608,"name":"Nicole S Nemychenkov","orcid":null,"position":4,"is_corresponding":false},{"id":691732,"name":"Kathleen S. Ensbey","orcid":null,"position":5,"is_corresponding":false},{"id":802059,"name":"Christine R. Schmidt","orcid":"0009-0003-2051-0825","position":6,"is_corresponding":false},{"id":886609,"name":"Samuel R.W. Legg","orcid":null,"position":7,"is_corresponding":false},{"id":831014,"name":"Melissa Comstock","orcid":"0009-0004-0393-9571","position":8,"is_corresponding":false},{"id":1206098,"name":"Julie R. Boiko","orcid":"0009-0008-1378-4752","position":9,"is_corresponding":false},{"id":1206099,"name":"Ethan Nelson","orcid":"0000-0002-2354-0945","position":10,"is_corresponding":false},{"id":886205,"name":"Shruti S. Bhise","orcid":"0009-0002-7826-8704","position":11,"is_corresponding":false},{"id":1206100,"name":"Alec B. Wilkens","orcid":"0000-0001-8721-9133","position":12,"is_corresponding":false},{"id":758907,"name":"Motoko Koyama","orcid":"0009-0003-6097-1204","position":13,"is_corresponding":false},{"id":268266,"name":"Madhav V. Dhodapkar","orcid":"0000-0002-8249-5988","position":14,"is_corresponding":false},{"id":336004,"name":"Marta Chesi","orcid":"0000-0002-4024-8225","position":15,"is_corresponding":false},{"id":232699,"name":"Stanley R. Riddell","orcid":"0000-0002-4688-9920","position":16,"is_corresponding":false},{"id":522226,"name":"Damian J. Green","orcid":"0000-0003-0477-1446","position":17,"is_corresponding":false},{"id":282793,"name":"Andrew Spencer","orcid":"0000-0002-0531-7424","position":18,"is_corresponding":false},{"id":94709,"name":"Scott N. Furlan","orcid":"0000-0003-3007-9840","position":19,"is_corresponding":false},{"id":242760,"name":"Geoffrey R. Hill","orcid":"0000-0003-2994-0429","position":20,"is_corresponding":false},{"id":243143,"name":"Simone A. Minnie","orcid":"0000-0002-1314-9264","position":0,"is_corresponding":true}],"reference_count":79,"raw_metadata":null,"created_at":"2026-07-19T01:57:02.483590Z","pmid":"38640253","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":[]}