{"doi":"10.1016/j.omton.2024.200839","title":"Exclusion of PD-1 from the immune synapse: A novel strategy to modulate T cell function","abstract":"Targeting immune checkpoint receptors on T cells is a common cancer treatment strategy. Frequently, this is accomplished through antibodies targeting the ligand of inhibitory co-receptors. Blocking the immune checkpoint PD-1 binding to its ligands PD-L1 and PD-L2 prevents downstream signaling and enhances anti-tumor T cell responses. This approach improves cancer patients' outcomes. However, only one-third of the patients respond to these treatments. To better understand the mechanism of anti-PD-1 antibodies, we explored the location of PD-1 within the immune synapse. Surprisingly, we discovered that anti-PD-1 antibodies, besides blocking the interaction between PD-1 and its ligands, also removed PD-1 from the synapse. We demonstrated a correlation between removing PD-1 from the synapse by anti-PD-1 antibodies and the extent of T cell activation. Interestingly, a short version of the anti-PD-1 antibody, F(ab′) 2 , failed to remove PD-1 from the synapse and activate T cells. Using the syngeneic tumor model, we showed a superior anti-tumor effect of the anti-PD-1 antibody over the shorter version of the same antibody. Our data indicate that anti-PD-1 antibodies activate T cells by removing PD-1 from the synapse, and changing the location of PD-1 or other immune receptors within the immune synapse could serve as an alternative, efficient approach to treat cancer.","journal":"Molecular Therapy Oncology","year":2024,"id":448810,"datarank":0.30561206366128174,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.03684814327707347,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.03684814327707347,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":3,"citers_with_citation_signal":3,"citers_with_endowment":3,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9539,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":715551,"name":"Shalom Lerrer","orcid":"0000-0003-3416-8568","position":1,"is_corresponding":false},{"id":950374,"name":"Matthieu Paiola","orcid":"0000-0002-3536-861X","position":2,"is_corresponding":false},{"id":886067,"name":"Emily K. Moore","orcid":"0000-0003-2186-5647","position":3,"is_corresponding":false},{"id":672411,"name":"Yevgeniya Gartshteyn","orcid":"0000-0001-5547-4658","position":4,"is_corresponding":false},{"id":903254,"name":"Ruijiang Song","orcid":null,"position":5,"is_corresponding":false},{"id":1179049,"name":"Michael Goeckeritz","orcid":null,"position":6,"is_corresponding":false},{"id":1268196,"name":"Matilda J Black","orcid":null,"position":7,"is_corresponding":false},{"id":716906,"name":"Shoiab Bukhari","orcid":"0000-0002-1172-7139","position":8,"is_corresponding":false},{"id":1179050,"name":"Xizi Hu","orcid":null,"position":9,"is_corresponding":false},{"id":672412,"name":"Adam Mor","orcid":"0000-0002-1065-2999","position":10,"is_corresponding":false},{"id":277555,"name":"Luke Hao","orcid":"0000-0003-4251-3595","position":0,"is_corresponding":true}],"reference_count":32,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:02:12.215092Z","pmid":"39072290","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":[]}