{"doi":"10.3389/fimmu.2025.1681777","title":"IFNγ-mediated suppression of alternative NF-κB in tumor-resident myeloid cells promotes selective recruitment of cytotoxic but not regulatory T cells","abstract":"cytotoxic T cells (CTLs) and low infiltration with regulatory T cells (Treg) predicts the patients' responses to immunotherapy and long-term outcomes. To identify the mechanisms regulating long-term stability of CTL infiltration, we analyzed the impact of CTL-produced cytokines on the TME by co-culturing patient-isolated ascites cells with activated T cells. Unexpectedly, we observed that activated CTLs selectively induce cytotoxic T cell-attracting chemokines but not chemokines that attract T regulatory cells in ovarian cancer TME and tumor-associated myeloid cells, resulting in recruitment of additional CTLs without Tregs. This selectivity resulted from the unique dependence of CCL22 induction on both canonical and alternative NF-κB and the suppression of alternative NF-κB signaling by T cell-released IFNγ. Our data demonstrate that T cell-produced IFNγ suppresses alternative NF-κB signaling in TME-associated myeloid cells, allowing for the induction of CTL-attracting chemokines with the concomitant suppression of Treg-attracting CCL22. These novel functions of IFNγ and activated T cells in regulating the balance between canonical and alternative NF-κB signaling in myeloid cells provide new opportunities to enhance and stabilize the selective CTL influx in the TME.","journal":"Frontiers in Immunology","year":2025,"id":577295,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9505,"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":563458,"name":"Ravikumar Muthuswamy","orcid":"0000-0002-1579-1664","position":1,"is_corresponding":false},{"id":1177893,"name":"Bowen Dong","orcid":"0000-0001-9895-2496","position":2,"is_corresponding":false},{"id":311537,"name":"Robert P. Edwards","orcid":"0000-0003-0370-1390","position":3,"is_corresponding":false},{"id":281558,"name":"Paweł Kaliński","orcid":"0000-0001-7025-3562","position":4,"is_corresponding":false},{"id":331392,"name":"Adam S. Brinkman","orcid":"0000-0002-8868-2290","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:58:04.622308Z","pmid":"41142824","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":[]}