{"doi":"10.1093/jimmun/vkaf314","title":"IL-15 complex enhances therapeutic efficacy of anti-PD-L1 in a T cell–dependent and NK cell–independent manner in a murine model of pancreatic ductal adenocarcinoma","abstract":"Pancreatic ductal adenocarcinoma (PDA) is a lethal malignancy resistant to therapy including immune checkpoint blockade (ICB). We previously showed that ICB selects for pancreatic tumor cells that are defective in IFN-γ-inducible MHC-I, prompting us to test the impact of IL-15 complex (IL-15C) in overcoming ICB resistance. Here, we show that IL-15C markedly expands circulating NK cells, CD8+ T cells, and CD4+Cxcr3+ T cells in an orthotopic pancreatic ductal adenocarcinoma (PDA) animal model. In tumors, IL-15C + anti-PD-L1 increased CD8+ T-cell effector cytokine production and interfered with T-cell exhaustion, including mitigating IL-10. In NK cells, IL-15C + anti-PD-L1 modulated NK cell IFN-γ production but did not alter Nkg2d, Nkg2a, Klrg1, IL-10, or granzyme B. IL-15C + anti-PD-L1 significantly prolonged animal survival, leading to tumor eradication in a subset of animals, whereas monotherapies only transiently prolonged survival. Therapeutic benefit was dependent on CD8+ T cells and independent of NK cells and Nkg2d. Together, our study supports that IL-15C improves anti-PD-L1 in PDA through sustaining antitumor T-cell function.","journal":"The Journal of Immunology","year":2025,"id":535451,"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":0.9496,"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":1143623,"name":"Alexander K. Tsai","orcid":"0000-0002-4014-1946","position":1,"is_corresponding":false},{"id":1383448,"name":"Madeline A. Ellefson","orcid":null,"position":2,"is_corresponding":false},{"id":658616,"name":"Zoe C. Schmiechen","orcid":"0000-0002-3403-6824","position":3,"is_corresponding":false},{"id":1383034,"name":"Brandon M. Larsen","orcid":"0009-0003-5647-3202","position":4,"is_corresponding":false},{"id":427690,"name":"Kristina S. Burrack","orcid":"0000-0002-6931-226X","position":5,"is_corresponding":false},{"id":513391,"name":"Ingunn M. Stromnes","orcid":"0000-0001-8120-4547","position":6,"is_corresponding":false},{"id":445732,"name":"Adam L. Burrack","orcid":"0000-0002-4001-7849","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":null,"created_at":"2026-07-19T02:51:56.297114Z","pmid":"41254945","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":[]}