{"doi":"10.1084/jem.20231242","title":"TCR ligand potency differentially impacts PD-1 inhibitory effects on diverse signaling pathways","abstract":"Checkpoint blockade revolutionized cancer therapy, but we still lack a quantitative, mechanistic understanding of how inhibitory receptors affect diverse signaling pathways. To address this issue, we developed and applied a fluorescent intracellular live multiplex signal transduction activity reporter (FILMSTAR) system to analyze PD-1-induced suppressive effects. These studies identified pathways triggered solely by TCR or requiring both TCR and CD28 inputs. Using presenting cells differing in PD-L1 and CD80 expression while displaying TCR ligands of distinct potency, we found that PD-1-mediated inhibition primarily targets TCR-linked signals in a manner highly sensitive to peptide ligand quality. These findings help resolve discrepancies in existing data about the site(s) of PD-1 inhibition in T cells while emphasizing the importance of neoantigen potency in controlling the effects of checkpoint therapy.","journal":"The Journal of Experimental Medicine","year":2023,"id":329532,"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":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9543,"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":1052272,"name":"Yuqi M. Cao","orcid":"0009-0002-1757-2649","position":1,"is_corresponding":false},{"id":820126,"name":"Xiang Zhao","orcid":"0000-0002-0043-324X","position":2,"is_corresponding":false},{"id":1052273,"name":"Edward C. Schrom","orcid":"0000-0002-1793-6433","position":3,"is_corresponding":false},{"id":468077,"name":"Dongya Jia","orcid":"0000-0002-6307-8580","position":4,"is_corresponding":false},{"id":1052274,"name":"Jian Song","orcid":"0000-0002-0289-3063","position":5,"is_corresponding":false},{"id":488943,"name":"Leah V. Sibener","orcid":"0000-0001-9737-8517","position":6,"is_corresponding":false},{"id":109712,"name":"Shen Dong","orcid":"0000-0001-8839-7046","position":7,"is_corresponding":false},{"id":264643,"name":"Ricardo A. Fernandes","orcid":"0000-0001-5343-3334","position":8,"is_corresponding":false},{"id":400350,"name":"Clinton J. Bradfield","orcid":"0000-0001-6410-3517","position":9,"is_corresponding":false},{"id":232579,"name":"Margery Smelkinson","orcid":"0000-0001-7777-5574","position":10,"is_corresponding":false},{"id":243363,"name":"Juraj Kabát","orcid":"0000-0001-8636-542X","position":11,"is_corresponding":false},{"id":688053,"name":"Jyh Liang Hor","orcid":"0000-0001-6721-4204","position":12,"is_corresponding":false},{"id":109653,"name":"Grégoire Altan‐Bonnet","orcid":"0000-0002-7283-3162","position":13,"is_corresponding":false},{"id":218189,"name":"K. Christopher García","orcid":"0000-0001-9273-0278","position":14,"is_corresponding":false},{"id":228444,"name":"Ronald N. Germain","orcid":"0000-0003-1495-9143","position":15,"is_corresponding":false},{"id":573676,"name":"Waipan Chan","orcid":"0000-0002-9109-6583","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-19T01:09:01.509601Z","pmid":"37796477","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":[]}