{"doi":"10.1101/2021.01.27.428467","title":"A reservoir of stem-like CD8 T cells in the tumor-draining lymph node maintains the ongoing anti-tumor immune response","abstract":"Abstract “Stem-like” TCF1 + CD8 + T cells (T SL ) are necessary for long-term maintenance of T cell responses and the efficacy of immunotherapy but, as tumors contain signals that should drive T-cell terminal-differentiation, how these cells are maintained in tumors remains unclear. We found that a small number of TCF1 + tumor-specific CD8 + T cells were present in tumors throughout development. Yet, most intratumoral T cells differentiated as tumors progressed, corresponding with an immunologic shift in the tumor microenvironment (TME) from “hot” to “cold”. By contrast, most tumor-specific CD8 + T cells in tumor-draining lymph nodes (dLNs) had functions and gene expression signatures similar to T SL from chronic LCMV infection and this population was stable over time, despite the changes in the TME. dLN T cells were the precursors of their more-differentiated intratumoral counterparts, and maintenance of TCF1 by intratumoral T cells required continuous migration from dLNs. Finally, T SL CD8 T cells were also present in LNs from lung adenocarcinoma patients, suggesting this population is also relevant in human disease. Thus, we propose that the dLN T SL reservoir has a critical function during tumor development in sustaining antitumor T cells during tumor development and protecting them from the terminal differentiation that occurs in the TME.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":214487,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.947,"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":564370,"name":"Manik Kuchroo","orcid":"0000-0001-7512-9739","position":1,"is_corresponding":false},{"id":804498,"name":"Aarthi Venkat","orcid":"0000-0003-0298-0172","position":2,"is_corresponding":false},{"id":302500,"name":"Achia Khatun","orcid":"0000-0003-0525-4774","position":3,"is_corresponding":false},{"id":273301,"name":"Jiawei Wang","orcid":"0000-0003-2627-4897","position":4,"is_corresponding":false},{"id":579398,"name":"Ivana William","orcid":"0000-0002-9040-2526","position":5,"is_corresponding":false},{"id":693511,"name":"Noah I. Hornick","orcid":"0000-0002-3503-7693","position":6,"is_corresponding":false},{"id":579999,"name":"Brittany Fitzgerald","orcid":null,"position":7,"is_corresponding":false},{"id":579397,"name":"Martina Damo","orcid":"0000-0002-7217-3221","position":8,"is_corresponding":false},{"id":302501,"name":"Moujtaba Y. Kasmani","orcid":"0000-0002-5753-5335","position":9,"is_corresponding":false},{"id":274504,"name":"Can Cui","orcid":"0000-0003-4736-4330","position":10,"is_corresponding":false},{"id":693509,"name":"Eric Fagerberg","orcid":"0000-0003-0313-3717","position":11,"is_corresponding":false},{"id":579403,"name":"Isabel Monroy","orcid":"0000-0003-3959-9324","position":12,"is_corresponding":false},{"id":808512,"name":"Amanda Hutchins","orcid":null,"position":13,"is_corresponding":false},{"id":579399,"name":"Julie F. Cheung","orcid":"0000-0003-1346-0930","position":14,"is_corresponding":false},{"id":372380,"name":"Gena G. Foster","orcid":"0000-0003-3482-0579","position":15,"is_corresponding":false},{"id":693510,"name":"Dylan L. Mariuzza","orcid":"0000-0002-9369-2514","position":16,"is_corresponding":false},{"id":2737,"name":"Luca Pinello","orcid":"0000-0003-1195-9607","position":17,"is_corresponding":false},{"id":302507,"name":"Weiguo Cui","orcid":"0000-0003-1562-9218","position":18,"is_corresponding":false},{"id":254926,"name":"Smita Krishnaswamy","orcid":"0000-0001-5823-1985","position":19,"is_corresponding":false},{"id":499816,"name":"Nikhil S. Joshi","orcid":"0000-0002-7045-7837","position":20,"is_corresponding":false},{"id":579400,"name":"Kelli A. Connolly","orcid":"0000-0002-3403-1150","position":0,"is_corresponding":true}],"reference_count":111,"raw_metadata":null,"created_at":"2026-07-18T23:52:46.604690Z","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":[]}