{"doi":"10.1073/pnas.2418985122","title":"Anti-CTLA-4 generates greater memory response than anti-PD-1 via TCF-1","abstract":"The effects of T cell differentiation arising from immune checkpoint inhibition targeting cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) on the immunological memory response remain unclear. Our investigation into the effects of anti-CTLA-4 and anti-PD-1 on memory T cell formation in mice reveals that memory T cells generated by anti-CTLA-4 exhibit greater expansion, cytokine production, and antitumor activity than those from anti-PD-1. Notably, anti-CTLA-4 preserves more T cell factor-1 (TCF-1)+ T cells during priming, while anti-PD-1 leads to more thymocyte selection-associated high mobility group box (TOX)+ T cells. Experiments using conditional Tcf7 - or Tox -knockout mice highlight that TCF-1 is essential for the memory response generated by anti-CTLA-4, whereas TOX deletion alone in T cells has no effect on the response to anti-PD-1. Deepening our understanding of how checkpoint inhibition affects memory response is crucial for advancing our understanding of the enduring impacts of these immunotherapies on the immune system.","journal":"Proceedings of the National Academy of Sciences","year":2025,"id":509966,"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":24,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9515,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":430765,"name":"Huey Liu","orcid":"0000-0002-0752-8348","position":1,"is_corresponding":false},{"id":830930,"name":"Didem Ağaç Çobanoğlu","orcid":"0000-0002-3493-7024","position":2,"is_corresponding":false},{"id":236799,"name":"Nana-Ama A.S. Anang","orcid":"0000-0002-8495-2978","position":3,"is_corresponding":false},{"id":236805,"name":"James J. Mancuso","orcid":"0000-0001-5776-8617","position":4,"is_corresponding":false},{"id":36451,"name":"E. John Wherry","orcid":"0000-0003-0477-1956","position":5,"is_corresponding":false},{"id":90470,"name":"James P. Allison","orcid":"0000-0001-8980-5697","position":6,"is_corresponding":false},{"id":1365975,"name":"Stephen Mok","orcid":null,"position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":null,"created_at":"2026-07-19T02:47:30.942539Z","pmid":"39786926","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":[]}