{"doi":"10.1136/jitc-2022-006221","title":"Irreversible electroporation augments β-glucan induced trained innate immunity for the treatment of pancreatic ductal adenocarcinoma","abstract":"BACKGROUND: Pancreatic cancer (PC) is a challenging diagnosis that is yet to benefit from the advancements in immuno-oncologic treatments. Irreversible electroporation (IRE), a non-thermal method of tumor ablation, is used in treatment of select patients with locally-advanced unresectable PC and has potentiated the effect of certain immunotherapies. Yeast-derived particulate β-glucan induces trained innate immunity and successfully reduces murine PC tumor burden. This study tests the hypothesis that IRE may augment β-glucan induced trained immunity in the treatment of PC. METHODS: mice. Tumor immune phenotypes were assessed by flow cytometry. Effect of oral β-glucan in the murine pancreas was evaluated and used in combination with IRE to treat PC. The peripheral blood of patients with PC taking oral β-glucan after IRE was evaluated by mass cytometry. RESULTS: IRE-ablated tumor cells elicited a potent trained response ex vivo and augmented antitumor functionality. In vivo, β-glucan in combination with IRE reduced local and distant tumor burden prolonging survival in a murine orthotopic PC model. This combination augmented immune cell infiltration to the PC tumor microenvironment and potentiated the trained response from tumor-infiltrating myeloid cells. The antitumor effect of this dual therapy occurred independent of the adaptive immune response. Further, orally administered β-glucan was identified as an alternative route to induce trained immunity in the murine pancreas and prolonged PC survival in combination with IRE. β-Glucan in vitro treatment also induced trained immunity in peripheral blood monocytes obtained from patients with treatment-naïve PC. Finally, orally administered β-glucan was found to significantly alter the innate cell landscape within the peripheral blood of five patients with stage III locally-advanced PC who had undergone IRE. CONCLUSIONS: These data highlight a relevant and novel application of trained immunity within the setting of surgical ablation that may stand to benefit patients with PC.","journal":"Journal for ImmunoTherapy of Cancer","year":2023,"id":325388,"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":31,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9526,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":848486,"name":"Rejeena Shrestha","orcid":"0000-0001-7642-6735","position":1,"is_corresponding":false},{"id":630850,"name":"Anne E. Geller","orcid":"0000-0002-7141-0803","position":2,"is_corresponding":false},{"id":659035,"name":"Shu Li","orcid":"0000-0003-0183-5459","position":3,"is_corresponding":false},{"id":616955,"name":"Diego E. Montoya–Durango","orcid":null,"position":4,"is_corresponding":false},{"id":250183,"name":"Chuanlin Ding","orcid":"0000-0001-9588-6403","position":5,"is_corresponding":false},{"id":252854,"name":"Xiaoling Hu","orcid":null,"position":6,"is_corresponding":false},{"id":1042987,"name":"Hong Li","orcid":"0000-0002-8240-7060","position":7,"is_corresponding":false},{"id":1043632,"name":"Aaron H. Puckett","orcid":null,"position":8,"is_corresponding":false},{"id":245765,"name":"Robert A. Mitchell","orcid":"0000-0002-8852-839X","position":9,"is_corresponding":false},{"id":1043633,"name":"Traci Hayat","orcid":null,"position":10,"is_corresponding":false},{"id":394555,"name":"Min Tan","orcid":"0000-0002-1986-8438","position":11,"is_corresponding":false},{"id":1042988,"name":"Yan Li","orcid":"0000-0002-9403-9533","position":12,"is_corresponding":false},{"id":7954,"name":"Kelly M. McMasters","orcid":"0000-0001-9554-3857","position":13,"is_corresponding":false},{"id":445524,"name":"Robert C.G. Martin","orcid":"0000-0002-5537-3387","position":14,"is_corresponding":false},{"id":250194,"name":"Jun Yan","orcid":"0000-0003-2922-422X","position":15,"is_corresponding":false},{"id":630852,"name":"Matthew R. Woeste","orcid":"0000-0001-5594-2888","position":0,"is_corresponding":true}],"reference_count":74,"raw_metadata":null,"created_at":"2026-07-19T01:08:22.919783Z","pmid":"37072351","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":[]}