{"doi":"10.1038/s41590-024-01999-3","title":"Dysfunction of exhausted T cells is enforced by MCT11-mediated lactate metabolism","abstract":"Abstract CD8 + T cells are critical mediators of antitumor immunity but differentiate into a dysfunctional state, known as T cell exhaustion, after persistent T cell receptor stimulation in the tumor microenvironment (TME). Exhausted T (T ex ) cells are characterized by upregulation of coinhibitory molecules and reduced polyfunctionality. T cells in the TME experience an immunosuppressive metabolic environment via reduced levels of nutrients and oxygen and a buildup of lactic acid. Here we show that terminally T ex cells uniquely upregulate Slc16a11 , which encodes monocarboxylate transporter 11 (MCT11). Conditional deletion of MCT11 in T cells reduced lactic acid uptake by T ex cells and improved their effector function. Targeting MCT11 with an antibody reduced lactate uptake specifically in T ex cells, which, when used therapeutically in tumor-bearing mice, resulted in reduced tumor growth. These data support a model in which T ex cells upregulate MCT11, rendering them sensitive to lactic acid present at high levels in the TME.","journal":"Nature Immunology","year":2024,"id":416414,"datarank":0.7485648880168105,"base_score":4.990432586778736,"endowment":4.990432586778736,"self_citation_contribution":0.7485648880168105,"citation_network_contribution":0.0,"self_endowment_contribution":0.7485648880168105,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":146,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.956,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":282225,"name":"Bingxian Xie","orcid":"0000-0001-9816-2670","position":1,"is_corresponding":false},{"id":823472,"name":"Konstantinos Lontos","orcid":"0000-0003-0216-3818","position":2,"is_corresponding":false},{"id":638506,"name":"Hector Nieves-Rosado","orcid":"0000-0001-8084-0728","position":3,"is_corresponding":false},{"id":1199657,"name":"Kellie Spahr","orcid":"0000-0002-4119-4994","position":4,"is_corresponding":false},{"id":918279,"name":"Supriya Joshi","orcid":"0000-0002-5205-3847","position":5,"is_corresponding":false},{"id":809372,"name":"B. Rhodes Ford","orcid":"0000-0001-8777-5244","position":6,"is_corresponding":false},{"id":1199658,"name":"Kevin Quann","orcid":"0000-0003-2213-3771","position":7,"is_corresponding":false},{"id":809373,"name":"Andrew Frisch","orcid":"0000-0002-0080-9147","position":8,"is_corresponding":false},{"id":1033246,"name":"Victoria Dean","orcid":"0009-0002-9136-3917","position":9,"is_corresponding":false},{"id":516811,"name":"Mary Philbin","orcid":null,"position":10,"is_corresponding":false},{"id":109265,"name":"Anthony R. Cillo","orcid":"0000-0002-3213-3129","position":11,"is_corresponding":false},{"id":526579,"name":"Sébastien Gingras","orcid":"0000-0003-2607-8642","position":12,"is_corresponding":false},{"id":282226,"name":"Amanda C. Poholek","orcid":"0000-0002-5587-8940","position":13,"is_corresponding":false},{"id":349057,"name":"Larry Kane","orcid":"0000-0001-5198-516X","position":14,"is_corresponding":false},{"id":841691,"name":"Dayana B. Rivadeneira","orcid":"0000-0001-9483-7036","position":15,"is_corresponding":false},{"id":237079,"name":"Greg M. Delgoffe","orcid":"0000-0002-2957-8135","position":16,"is_corresponding":false},{"id":614548,"name":"Ronal M. Peralta","orcid":"0000-0002-2863-0157","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:56:20.964471Z","pmid":"39516648","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":[]}