{"doi":"10.1101/2020.09.30.321240","title":"Circulating Clonally Expanded T Cells Reflect Functions of Tumor Infiltrating T Cells","abstract":"Abstract Understanding the relationship between tumor and peripheral immune environments could allow longitudinal immune monitoring in cancer. Here, we examined whether T cells that share the same TCRαβ and are found in both tumor and blood can be interrogated to gain insight into the ongoing tumor T cell response. Paired transcriptome and TCRαβ repertoire of circulating and tumor-infiltrating T cells were analyzed from matched tumor and blood from patients with metastatic melanoma at the single cell level. We found that in circulating T cells matching clonally expanded tumor-infiltrating T cells (circulating TILs), gene signatures of effector functions, but not terminal exhaustion, reflect those observed in the tumor. In contrast, features of exhaustion are displayed predominantly by T cells present only in tumor. Finally, genes associated with a high degree of blood-tumor TCR sharing were overexpressed in tumor tissue after immunotherapy. These data demonstrate that circulating TILs, identified by TCRs shared with T cells in tumors, have unique transcriptional expression patterns that may have utility for the interrogation of T cell function in cancer immunotherapy. Summary Combining transcriptomic and TCRαβ repertoire analysis of circulating and tumor-infiltrating CD8 T cells from patients with metastatic melanoma, we identify a blood-based population with effector properties that reflect those of clonally related tumor-resident T cells.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":123032,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9412,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":291529,"name":"Pierre‐Paul Axisa","orcid":"0000-0003-1446-3922","position":1,"is_corresponding":false},{"id":291530,"name":"Benjamin Y. Lu","orcid":"0000-0001-8764-8384","position":2,"is_corresponding":false},{"id":291531,"name":"Brian Harnett","orcid":"0000-0003-3606-1094","position":3,"is_corresponding":false},{"id":291532,"name":"Shlomit Jessel","orcid":"0000-0001-8489-0351","position":4,"is_corresponding":false},{"id":69461,"name":"Le Zhang","orcid":"0000-0002-4860-831X","position":5,"is_corresponding":false},{"id":261878,"name":"Khadir Raddassi","orcid":"0000-0002-2383-9744","position":6,"is_corresponding":false},{"id":291533,"name":"Lin Zhang","orcid":"0000-0002-0418-5706","position":7,"is_corresponding":false},{"id":291534,"name":"Kelly Olino","orcid":"0000-0001-6209-5218","position":8,"is_corresponding":false},{"id":291535,"name":"James Clune","orcid":"0000-0002-2398-4634","position":9,"is_corresponding":false},{"id":34472,"name":"Meromit Singer","orcid":"0000-0002-1755-3598","position":10,"is_corresponding":false},{"id":226323,"name":"Harriet M. Kluger","orcid":"0000-0002-4932-9873","position":11,"is_corresponding":false},{"id":37332,"name":"David A. Hafler","orcid":"0000-0003-4664-535X","position":12,"is_corresponding":false},{"id":291528,"name":"Liliana E. Lucca","orcid":"0000-0002-5109-0128","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-18T23:14:55.385653Z","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":[]}