{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Manfredi F"],"funding":["Academy of Finland","Associazione Italiana per la Ricerca sul Cancro","Italian Ministry of Health and Alliance Against Cancer (Ricerca Corrente","Italian Ministry of Education, University and Research"],"pagination":["eadg8014"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10691777"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["9(48)"],"pubmed_abstract":["To study and then harness the tumor-specific T cell dynamics after allogeneic hematopoietic stem cell transplant, we typed the frequency, phenotype, and function of lymphocytes directed against tumor-associated antigens (TAAs) in 39 consecutive transplanted patients, for 1 year after transplant. We showed that TAA-specific T cells circulated in 90% of patients but display a limited effector function associated to an exhaustion phenotype, particularly in the subgroup of patients deemed to relapse, where exhausted stem cell memory T cells accumulated. Accordingly, cancer-specific cytolytic functions were relevant only when the TAA-specific T cell receptors (TCRs) were transferred into healthy, genome-edited T cells. We then exploited trogocytosis and ligandome-on-chip technology to unveil the specificities of tumor-specific TCRs retrieved from the exhausted T cell pool. Overall, we showed that harnessing circulating TAA-specific and exhausted T cells allow to isolate TCRs against TAAs and previously not described acute myeloid leukemia antigens, potentially relevant for T cell-based cancer immunotherapy."],"journal":["Science advances"],"pubmed_title":["Harnessing T cell exhaustion and trogocytosis to isolate patient-derived tumor-specific TCR."],"pmcid":["PMC10691777"],"funding_grant_id":["RCR-2019-23669115","PRIN 2017WC8499","309608 AND 325222","AIRC-IG 18458 AND AIRC 5 PER MILLE 22737"],"pubmed_authors":["Manfredi F","Feola S","Balestrieri C","Cianciotti BC","Abbati D","Lehtio J","Cerullo V","Magnani Z","Ciceri F","Vago L","Bonini C","Tassi E","Sikanen TM","Potenza A","Punta M","Marzuttini F","Camisa B","Stasi L","Casucci M","Noviello M","Haapala MJ","Mastaglio S","Ruggiero E","Toffalori C","Branca RM","Tiziano E","Buonanno S","Lupo-Stanghellini MT"],"additional_accession":[]},"is_claimable":false,"name":"Harnessing T cell exhaustion and trogocytosis to isolate patient-derived tumor-specific TCR.","description":"To study and then harness the tumor-specific T cell dynamics after allogeneic hematopoietic stem cell transplant, we typed the frequency, phenotype, and function of lymphocytes directed against tumor-associated antigens (TAAs) in 39 consecutive transplanted patients, for 1 year after transplant. We showed that TAA-specific T cells circulated in 90% of patients but display a limited effector function associated to an exhaustion phenotype, particularly in the subgroup of patients deemed to relapse, where exhausted stem cell memory T cells accumulated. Accordingly, cancer-specific cytolytic functions were relevant only when the TAA-specific T cell receptors (TCRs) were transferred into healthy, genome-edited T cells. We then exploited trogocytosis and ligandome-on-chip technology to unveil the specificities of tumor-specific TCRs retrieved from the exhausted T cell pool. Overall, we showed that harnessing circulating TAA-specific and exhausted T cells allow to isolate TCRs against TAAs and previously not described acute myeloid leukemia antigens, potentially relevant for T cell-based cancer immunotherapy.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Dec","modification":"2026-06-23T03:17:20.241Z","creation":"2025-02-19T01:18:09.597Z"},"accession":"S-EPMC10691777","cross_references":{"pubmed":["38039364"],"doi":["10.1126/sciadv.adg8014"]}}