{"doi":"10.1084/jem.20212218","title":"Platelet-derived TLT-1 promotes tumor progression by suppressing CD8+ T cells","abstract":"Current understanding of tumor immunosuppressive mechanisms forms the basis for modern day immunotherapies. Immunoregulatory role of platelets in cancer remains largely elusive. Platelets from non-small cell lung cancer (NSCLC) patients revealed a distinct activation phenotype. TREM-like transcript 1 (TLT-1), a platelet protein, was increased along with enhanced extracellular release from NSCLC platelets. The increased platelet TLT-1 was also evident in humanized mice with patient-derived tumors. In immunocompetent mice with syngeneic tumors, TLT-1 binding to T cells, in vivo, led to suppression of CD8 T cells, promoting tumor growth. We identified direct interaction between TLT-1 and CD3ε on T cells, implicating the NF-κB pathway in CD8 T cell suppression. Anti-TLT-1 antibody rescued patients' T cells from platelet-induced suppression ex vivo and reduced tumors in mice in vivo. Clinically, higher TLT-1 correlated with reduced survival of NSCLC patients. Our findings thus identify TLT-1 as a platelet-derived immunosuppressor that suppresses CD8 T cells and demonstrate its therapeutic and prognostic significance in cancer.","journal":"The Journal of Experimental Medicine","year":2022,"id":241355,"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":42,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9635,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":228513,"name":"Kanika Jain","orcid":"0000-0003-1826-4402","position":1,"is_corresponding":false},{"id":824000,"name":"Timur O. Yarovinsky","orcid":"0000-0003-0531-2559","position":2,"is_corresponding":false},{"id":657016,"name":"Michael Chiorazzi","orcid":"0000-0001-6289-3893","position":3,"is_corresponding":false},{"id":380710,"name":"Jing Du","orcid":"0000-0001-6946-4653","position":4,"is_corresponding":false},{"id":870207,"name":"Cecilia Castro","orcid":"0000-0003-1180-9780","position":5,"is_corresponding":false},{"id":271654,"name":"Julian L. Griffin","orcid":"0000-0003-1336-7744","position":6,"is_corresponding":false},{"id":870208,"name":"Asawari Korde","orcid":"0000-0001-6388-7292","position":7,"is_corresponding":false},{"id":228516,"name":"Kathleen A. Martin","orcid":"0000-0002-1748-0034","position":8,"is_corresponding":false},{"id":352844,"name":"S. Takyar","orcid":"0000-0003-1369-1544","position":9,"is_corresponding":false},{"id":80236,"name":"Richard A. Flavell","orcid":"0000-0003-4461-0778","position":10,"is_corresponding":false},{"id":557793,"name":"Abhijit A. Patel","orcid":"0000-0003-3943-5610","position":11,"is_corresponding":false},{"id":106673,"name":"John Hwa","orcid":"0000-0001-7366-2628","position":12,"is_corresponding":false},{"id":228512,"name":"Tarun Tyagi","orcid":"0000-0002-3043-3830","position":0,"is_corresponding":true}],"reference_count":104,"raw_metadata":null,"created_at":"2026-07-19T00:22:56.227656Z","pmid":"36305874","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":[]}