{"doi":"10.1101/2020.03.12.989731","title":"IRF8 Governs Tumor-Associated Macrophage Control of T Cell Exhaustion","abstract":"Summary Tumor progression is associated with overstimulation of cytotoxic T lymphocytes (CTLs), resulting in a dysfunctional state of exhaustion. How T cell exhaustion is elicited in the tumor remains poorly understood. Here we show that tumor-associated macrophages (TAMs) present cancer cell antigen and induce CTL exhaustion through a gene expression program dependent on the transcription factor interferon regulatory factor-8 (IRF8). In a transgenic model of murine breast cancer, CTL priming was supported by IRF8-dependent dendritic cells; yet, CTL exhaustion required TAM expression of IRF8, and its ablation suppressed tumor growth. An analysis of the highly immune-infiltrated human renal cell carcinoma tumors revealed abundant TAMs that expressed IRF8 and were enriched for an IRF8 gene expression signature. The IRF8 signature co-segregated with T cell exhaustion markers and was negatively associated with long-term patient survival. Thus, CTL exhaustion is promoted by TAMs via IRF8, and this crosstalk may be disrupted in TAM-targeted therapies.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":122632,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.949,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":244688,"name":"Fengshen Kuo","orcid":"0000-0003-1797-2896","position":1,"is_corresponding":false},{"id":461679,"name":"Ming Liu","orcid":"0000-0003-4548-2683","position":2,"is_corresponding":false},{"id":240587,"name":"Kristelle J. Capistrano","orcid":"0000-0003-4349-9924","position":3,"is_corresponding":false},{"id":565265,"name":"Mytrang Do","orcid":null,"position":4,"is_corresponding":false},{"id":251300,"name":"Ruth A. Franklin","orcid":"0000-0002-6563-6187","position":5,"is_corresponding":false},{"id":564363,"name":"Xiaodi Wu","orcid":"0000-0003-0886-8640","position":6,"is_corresponding":false},{"id":564364,"name":"Emily R. Kansler","orcid":"0000-0001-9601-4084","position":7,"is_corresponding":false},{"id":244690,"name":"Raghvendra M. Srivastava","orcid":"0000-0001-6545-3957","position":8,"is_corresponding":false},{"id":248136,"name":"Tanaya A. Purohit","orcid":null,"position":9,"is_corresponding":false},{"id":348093,"name":"Alejandro Sánchez","orcid":"0000-0002-9054-7346","position":10,"is_corresponding":false},{"id":564365,"name":"Lynda Vuong","orcid":"0000-0002-3277-0064","position":11,"is_corresponding":false},{"id":56492,"name":"Chirag Krishna","orcid":"0000-0002-9166-4632","position":12,"is_corresponding":false},{"id":564366,"name":"Herbert C. Morse","orcid":"0000-0002-9331-3705","position":13,"is_corresponding":false},{"id":249414,"name":"James J. Hsieh","orcid":"0000-0003-3595-0551","position":14,"is_corresponding":false},{"id":69956,"name":"Timothy A. Chan","orcid":"0000-0002-9265-0283","position":15,"is_corresponding":false},{"id":227901,"name":"Kenneth M. Murphy","orcid":"0000-0002-3505-9630","position":16,"is_corresponding":false},{"id":39515,"name":"James Moon","orcid":"0000-0001-8071-1491","position":17,"is_corresponding":false},{"id":90737,"name":"A. Ari Hakimi","orcid":"0000-0002-0930-8824","position":18,"is_corresponding":false},{"id":240589,"name":"Ming O. Li","orcid":"0000-0002-1383-0535","position":19,"is_corresponding":false},{"id":240583,"name":"Briana G. Nixon","orcid":"0000-0001-7334-9404","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-18T23:14:55.385653Z","pmid":null,"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":[]}