{"doi":"10.1101/2023.09.26.559470","title":"Multimodal delineation of a layer of effector function among exhausted CD8 T cells in tumors","abstract":"Abstract The anti-tumor function of CD8 T cells is limited through well-established pathways of T cell exhaustion (T EX ). Strategies to capture emergent functional states amongst this dominant trajectory of dysfunction are necessary to find pathways to durable anti-tumor immunity. By leveraging transcriptional reporting (by the fluorescent protein TFP) of the T cell activation marker Cd69, related to upstream AP-1 transcription factors, we define a classifier for potent versus sub-optimal CD69+ activation states arising from T cell stimulation. In tumors, this delineation acts an additional functional readout along the T EX differentiation trajectory, within and across T EX subsets, marked by enhanced effector cytokine and granzyme B production. The more potent state remains differentially prominent in a T cell-mediated tumor clearance model, where they also show increased engagement in the microenvironment and are superior in tumor cell killing. Employing multimodal CITE-Seq in human head and neck tumors enables a similar strategy to identify Cd69RNA hi CD69+ cells that also have enhanced functional features in comparison to Cd69RNA lo CD69+ cells, again within and across intratumoral CD8 T cell subsets. Refining the contours of the T cell functional landscape in tumors in this way paves the way for the identification of rare exceptional effectors, with imminent relevance to cancer treatment. Graphical Abstract","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":392636,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.951,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":561687,"name":"Molly Bassette","orcid":"0000-0001-8658-8148","position":1,"is_corresponding":false},{"id":553724,"name":"Kenneth H. Hu","orcid":"0000-0002-0294-0202","position":2,"is_corresponding":false},{"id":1166220,"name":"Lomax F. Pass","orcid":"0000-0003-1198-4087","position":3,"is_corresponding":false},{"id":553723,"name":"Tristan Courau","orcid":"0000-0003-1819-9516","position":4,"is_corresponding":false},{"id":620243,"name":"Bushra Samad","orcid":"0000-0002-2893-0897","position":5,"is_corresponding":false},{"id":553722,"name":"Alexis J. Combes","orcid":"0000-0002-9110-6542","position":6,"is_corresponding":false},{"id":1014074,"name":"Vrinda Johri","orcid":"0000-0001-7341-4675","position":7,"is_corresponding":false},{"id":559268,"name":"Brittany Davidson","orcid":"0000-0003-3538-2822","position":8,"is_corresponding":false},{"id":1014073,"name":"Katherine C. Wai","orcid":"0000-0001-8180-4542","position":9,"is_corresponding":false},{"id":403109,"name":"Patrick K. Ha","orcid":"0000-0003-0306-6147","position":10,"is_corresponding":false},{"id":570769,"name":"Grace A. Hernandez","orcid":"0000-0001-6494-6194","position":11,"is_corresponding":false},{"id":1162897,"name":"Itzia Zaleta-Linares","orcid":null,"position":12,"is_corresponding":false},{"id":240181,"name":"Matthew F. Krummel","orcid":"0000-0001-7915-3533","position":13,"is_corresponding":false},{"id":553725,"name":"Arja Ray","orcid":"0000-0003-2305-2324","position":0,"is_corresponding":true}],"reference_count":75,"raw_metadata":null,"created_at":"2026-07-19T01:18:56.730121Z","pmid":"37808790","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":[]}