{"doi":"10.26508/lsa.202503335","title":"Loss of <i>Bcl6</i> promotes antitumor immunity by activating glycolysis to rescue CD8 T-cell function","abstract":"T cells are one of the most powerful weapons to fight cancer; however, T-cell exhaustion and dysfunction restrict their long-lasting function in antitumor immunity. B-cell lymphoma 6 (BCL6) has many functions in CD8 T cells; however, it is unclear how it regulates the effector function and exhaustion of CD8 cells. Overall, a low level of BCL6 mRNA in human cancer samples is associated with better outcomes, but high expression of BCL6 is specifically observed in cytotoxic CD8 T cells. We found that BCL6 deficiency in activated CD8 T cells enhanced tumor repression in multiple mouse models. More IL-2–expressing CD8 T cells and reduced proportions of exhausted or dysfunctional CD8 T cells were detected within tumors when Bcl6 was knocked out upon T-cell activation. Glycolysis was promoted, and GLUT3 expression was derepressed in BCL6-deficient CD8 T cells. The BCL6 inhibitor Fx1 promoted antitumor immunity in a T cell–dependent manner. These findings suggest a novel pathway to restore effector function of CD8 T cells by changing their energy use pathways to facilitate long-term tumor resistance.","journal":"Life Science Alliance","year":2025,"id":529187,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9491,"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":731299,"name":"Yunqiao Li","orcid":"0000-0001-9937-1634","position":1,"is_corresponding":false},{"id":326432,"name":"Jia Ning","orcid":"0000-0002-2827-6338","position":2,"is_corresponding":false},{"id":297046,"name":"Jenny Tuyet Tran","orcid":null,"position":3,"is_corresponding":false},{"id":296040,"name":"Tanya R. Blane","orcid":"0000-0001-8132-3167","position":4,"is_corresponding":false},{"id":731916,"name":"Raag Bhargava","orcid":null,"position":5,"is_corresponding":false},{"id":731297,"name":"Zhe Huang","orcid":"0000-0002-1312-5457","position":6,"is_corresponding":false},{"id":490358,"name":"Changchun Xiao","orcid":"0000-0001-8754-3208","position":7,"is_corresponding":false},{"id":109546,"name":"David Nemazee","orcid":"0000-0002-4769-6311","position":8,"is_corresponding":false},{"id":1195966,"name":"Fangkun Luan","orcid":null,"position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-19T02:50:56.971987Z","pmid":"41145211","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":[]}