{"doi":"10.3389/fimmu.2021.738958","title":"Targeting Cbx3/HP1γ Induces LEF-1 and IL-21R to Promote Tumor-Infiltrating CD8 T-Cell Persistence","abstract":"Immune checkpoint blockade (ICB) relieves CD8 + T-cell exhaustion in most mutated tumors, and TCF-1 is implicated in converting progenitor exhausted cells to functional effector cells. However, identifying mechanisms that can prevent functional senescence and potentiate CD8 + T-cell persistence for ICB non-responsive and resistant tumors remains elusive. We demonstrate that targeting Cbx3 /HP1γ in CD8 + T cells augments transcription initiation and chromatin remodeling leading to increased transcriptional activity at Lef1 and Il21r . LEF-1 and IL-21R are necessary for Cbx3 /HP1γ-deficient CD8 + effector T cells to persist and control ovarian cancer, melanoma, and neuroblastoma in preclinical models. The enhanced persistence of Cbx3 /HP1γ-deficient CD8 + T cells facilitates remodeling of the tumor chemokine/receptor landscape ensuring their optimal invasion at the expense of CD4 + Tregs. Thus, CD8 + T cells heightened effector function consequent to Cbx3 /HP1γ deficiency may be distinct from functional reactivation by ICB, implicating Cbx3 /HP1γ as a viable cancer T-cell-based therapy target for ICB resistant, non-responsive solid tumors.","journal":"Frontiers in Immunology","year":2021,"id":181931,"datarank":0.41588830833596724,"base_score":2.772588722239781,"endowment":2.772588722239781,"self_citation_contribution":0.41588830833596724,"citation_network_contribution":0.0,"self_endowment_contribution":0.41588830833596724,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9473,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":571307,"name":"Ngoc T. Ha","orcid":"0000-0001-6640-0830","position":1,"is_corresponding":false},{"id":734286,"name":"Ngan K. Tran","orcid":null,"position":2,"is_corresponding":false},{"id":733611,"name":"Andrew G. Newman","orcid":"0000-0002-0222-9162","position":3,"is_corresponding":false},{"id":326034,"name":"Katharine M. Esselen","orcid":"0000-0002-6750-8699","position":4,"is_corresponding":false},{"id":326032,"name":"John L. Dalrymple","orcid":"0000-0001-5183-1937","position":5,"is_corresponding":false},{"id":678785,"name":"Eva M. Schmelz","orcid":"0000-0002-3374-5266","position":6,"is_corresponding":false},{"id":471420,"name":"Avinash Bhandoola","orcid":"0000-0002-4657-8372","position":7,"is_corresponding":false},{"id":271042,"name":"Hai‐Hui Xue","orcid":"0000-0002-9163-7669","position":8,"is_corresponding":false},{"id":733612,"name":"Prim B. Singh","orcid":"0000-0002-9571-0974","position":9,"is_corresponding":false},{"id":734287,"name":"To‐Ha Thai","orcid":null,"position":10,"is_corresponding":false},{"id":419233,"name":"Phuong Le","orcid":null,"position":0,"is_corresponding":true}],"reference_count":85,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:48:09.223560Z","pmid":"34721405","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":[]}