{"doi":"10.1016/j.celrep.2023.112436","title":"PSGL-1 attenuates early TCR signaling to suppress CD8+ T cell progenitor differentiation and elicit terminal CD8+ T cell exhaustion","abstract":"PSGL-1 (P-selectin glycoprotein-1) is a T cell-intrinsic checkpoint regulator of exhaustion with an unknown mechanism of action. Here, we show that PSGL-1 acts upstream of PD-1 and requires co-ligation with the T cell receptor (TCR) to attenuate activation of mouse and human CD8 + T cells and drive terminal T cell exhaustion. PSGL-1 directly restrains TCR signaling via Zap70 and maintains expression of the Zap70 inhibitor Sts-1. PSGL-1 deficiency empowers CD8 + T cells to respond to low-affinity TCR ligands and inhibit growth of PD-1-blockade-resistant melanoma by enabling tumor-infiltrating T cells to sustain an elevated metabolic gene signature supportive of increased glycolysis and glucose uptake to promote effector function. This outcome is coupled to an increased abundance of CD8 + T cell stem cell-like progenitors that maintain effector functions. Additionally, pharmacologic blockade of PSGL-1 curtails T cell exhaustion, indicating that PSGL-1 represents an immunotherapeutic target for PD-1-blockade-resistant tumors.","journal":"Cell Reports","year":2023,"id":324274,"datarank":0.5333022092234121,"base_score":3.5553480614894135,"endowment":3.5553480614894135,"self_citation_contribution":0.5333022092234121,"citation_network_contribution":0.0,"self_endowment_contribution":0.5333022092234121,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":34,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9541,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1040243,"name":"Dennis C. Otero","orcid":"0000-0001-5149-8062","position":1,"is_corresponding":false},{"id":922462,"name":"Eun‐Ah Bae","orcid":"0000-0002-9413-2543","position":2,"is_corresponding":false},{"id":1040244,"name":"Christopher J. Stairiker","orcid":"0000-0002-8503-0983","position":3,"is_corresponding":false},{"id":1040245,"name":"Ashley B. Palete","orcid":"0000-0002-4480-2561","position":4,"is_corresponding":false},{"id":1040246,"name":"Hannah A. Faso","orcid":"0000-0002-2884-8746","position":5,"is_corresponding":false},{"id":299186,"name":"Michelle Lin","orcid":"0000-0001-9342-4221","position":6,"is_corresponding":false},{"id":888337,"name":"Monique L. Henriquez","orcid":"0000-0001-5684-5959","position":7,"is_corresponding":false},{"id":367562,"name":"Sreeja Biswas Roy","orcid":"0000-0003-0002-542X","position":8,"is_corresponding":false},{"id":27570,"name":"Hyungseok Seo","orcid":"0000-0002-6632-1208","position":9,"is_corresponding":false},{"id":995088,"name":"Lei Xue","orcid":"0000-0002-9558-9641","position":10,"is_corresponding":false},{"id":941002,"name":"Eric S. Wang","orcid":"0000-0002-6250-9748","position":11,"is_corresponding":false},{"id":1040953,"name":"Savio Chow","orcid":null,"position":12,"is_corresponding":false},{"id":661846,"name":"Roberto Tinoco","orcid":"0000-0001-5420-9692","position":13,"is_corresponding":false},{"id":1040954,"name":"Gregory A. Daniels","orcid":null,"position":14,"is_corresponding":false},{"id":4939,"name":"Kevin Y. Yip","orcid":"0000-0001-5516-9944","position":15,"is_corresponding":false},{"id":259808,"name":"Alexandre Rosa Campos","orcid":"0000-0003-3988-7764","position":16,"is_corresponding":false},{"id":305691,"name":"Jun Yin","orcid":"0000-0003-4543-1229","position":17,"is_corresponding":false},{"id":227838,"name":"Peter D. Adams","orcid":"0000-0002-0684-1770","position":18,"is_corresponding":false},{"id":304132,"name":"Anjana Rao","orcid":"0000-0002-1870-1775","position":19,"is_corresponding":false},{"id":464035,"name":"Linda M. Bradley","orcid":"0000-0002-8697-8565","position":20,"is_corresponding":false},{"id":933670,"name":"Jennifer L. Hope","orcid":"0000-0002-2363-5442","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:08:11.275604Z","pmid":"37115668","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":[]}