{"doi":"10.4049/jimmunol.2200317","title":"Cutting Edge: Promoting T Cell Factor 1+ T Cell Self-Renewal to Improve Programmed Cell Death Protein 1 Blockade","abstract":"Abstract Immune checkpoint blockade is limited by resistance to treatment, with many patients not achieving durable antitumor responses. Self-renewing (T cell factor 1+ [TCF1+]) CD8+ T cells have recently been implicated in efficacy of anti–programmed cell death protein 1 (anti–PD-1). Mice challenged with syngeneic tumors were treated with anti–PD-1 and/or a reversible inhibitor of PI3K δ, designed to promote T cell self-renewal. Growth of tumors in untreated mice was characterized by waning proportions of TCF1+ T cells, suggesting self-renewing T cells become limiting for successful immunotherapy. Higher proportions of TCF1+ T cells in tumor and blood correlated with better control of tumor growth. Combining anti–PD-1 and inhibitor of PI3K δ conferred superior protection compared with either monotherapy and was associated with higher frequency of TCF1+ T cells in tumor and blood compared with anti–PD-1 alone. These findings reveal predictive importance of self-renewing T cells in anti-tumor immunity and suggest that resistance-directed strategies to enhance T cell self-renewal could potentiate the efficacy of PD-1 blockade.","journal":"The Journal of Immunology","year":2022,"id":273007,"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":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9479,"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":316651,"name":"Robert S. Washburn","orcid":"0000-0002-3533-951X","position":1,"is_corresponding":false},{"id":853171,"name":"Rohan Maniar","orcid":"0000-0002-6089-2237","position":2,"is_corresponding":false},{"id":842250,"name":"Michael Mu","orcid":"0000-0003-4035-5298","position":3,"is_corresponding":false},{"id":531859,"name":"Olivia R. Ringham","orcid":"0000-0001-6715-8599","position":4,"is_corresponding":false},{"id":909234,"name":"Radomir Kratchmarov","orcid":"0000-0002-6796-8564","position":5,"is_corresponding":false},{"id":688203,"name":"Brian S. Henick","orcid":"0000-0003-2681-0805","position":6,"is_corresponding":false},{"id":604503,"name":"Steven L. Reiner","orcid":"0000-0002-1635-8619","position":7,"is_corresponding":false},{"id":909233,"name":"Peter H. Wang","orcid":"0000-0002-5922-5111","position":0,"is_corresponding":true}],"reference_count":32,"raw_metadata":null,"created_at":"2026-07-19T00:27:52.048702Z","pmid":"35905999","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":[]}