{"doi":"10.1101/2021.10.31.466532","title":"Pan-cancer mapping of single T cell profiles reveals a TCF1:CXCR6-CXCL16 regulatory axis essential for effective anti-tumor immunity","abstract":"Unleashing cytotoxic CD8 + T cells for effective cancer treatment requires understanding T cell states across different tumor microenvironments. Here, we developed an algorithm to recover both shared and tumor type specific programs and used it to analyze a scRNA-seq compendium of 38,852 CD8 + T cells from 141 patients spanning nine different human cancers. We uncovered a pan-cancer T cell dysfunction program that was predictive of clinical responses to immunotherapy and highlighted CXCR6 as a pan-cancer marker of dysfunctional T cells. In mouse models, CXCR6 increased following checkpoint blockade and was repressed by TCF1. Its ligand, CXCL16, was expressed primarily by myeloid cells, and was co-regulated with antigen presentation genes. CXCR6 deletion decreased Tox, CX3CR1, and Bcl2 expression, predisposing dysfunctional PD-1 + Tim3 + CD8 + T cells to apoptosis, and compromising tumor growth control. Our approach discovered a TCF1:CXCR6-CXCL16 regulatory axis essential for effective anti-tumor immunity, revealing a new perspective on T cell dysfunction and new opportunities for modulating this cell state.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":11938,"datarank":0.3453877639491069,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.0,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0803,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-10-31","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":16696,"name":"Katherine Tooley","orcid":"0000-0003-0587-0358","position":1,"is_corresponding":false},{"id":50393,"name":"Giulia Escobar","orcid":"0000-0001-9177-0251","position":2,"is_corresponding":false},{"id":95636,"name":"Gitanjali Dandekar","orcid":null,"position":3,"is_corresponding":false},{"id":7864,"name":"Asaf Madi","orcid":"0000-0003-3441-3228","position":4,"is_corresponding":false},{"id":95637,"name":"Ella Goldschmidt","orcid":"0000-0003-1876-487X","position":5,"is_corresponding":false},{"id":59684,"name":"Conner D. Lambden","orcid":null,"position":6,"is_corresponding":false},{"id":3016,"name":"Ana. C. Anderson","orcid":"0000-0002-0877-2932","position":8,"is_corresponding":false},{"id":29633,"name":"Prisca Liberali","orcid":"0000-0003-0695-6081","position":9,"is_corresponding":false},{"id":5605,"name":"Livnat Jerby‐Arnon","orcid":"0009-0003-9926-4398","position":10,"is_corresponding":false},{"id":2697,"name":"Orit Rozenblatt–Rosen","orcid":"0000-0001-6313-3570","position":11,"is_corresponding":false},{"id":5594,"name":"Livnat Jerby-Arnon","orcid":"0000-0002-4037-386X","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"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":[]}