• Robert Cg Martin, Yan Li, Emily A Shore, Danial A Malik, Hong Li, Xiaoling Hu, Traci Hayat, Min Tan, Kelly M McMasters, and Jun Yan.
• Division of Surgical Oncology, The Hiram C. Polk Jr., MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY, USA.
• J. Am. Coll. Surg. 2025 Jan 22.

IntroductionIrreversible electroporation(IRE) has augmented the effects of certain immunotherapies in pancreatic cancer(PDA). Yeast-derived particulate beta-glucan induces trained innate immunity and has successfully reduces murine PC tumor burden. This is a Phase II study to test the hypothesis that IRE may augment beta-glucan induced trained immunity in patients with PDA.MethodsPhase II clinical trial (NCT03080974), surgical ablative IRE was performed on clinical stage-III PDA followed by oral beta-Glucan administration for 12-months or until disease recurrence. Peripheral blood was taken pre-op, 14-days, and every 3-months and was evaluated by mass cytometry and compared to patients who received IRE alone.ResultsThirty consecutive patients with pre-operative clinical stage-III PDA were treated with IRE and then initiated on oral beta-glucan post-operatively was compared to 20 patients treated with IRE alone. There were no dose limiting toxicities with oral beta-glucan and compliance with therapy was 96% in all patients. Seven(23%) patients developed grade 3/4 treatment related adverse events(AEs) at 90-days; none required a dose modification of oral beta-glucan. Median disease-free interval of 18 months (range 6-48), with a median overall survival of 32.5 months(range 4-53). At 12-months post IRE, immunophenotyping was demonstrated a significant effect with improvement in the IRE-Beta-Glucan treated group. This also resulted in a significant decrease on naïve CD4 and CD8 T cells with increased CD4 and CD8 terminal effector cells in the IRE-Beta glucan treated group, which correlated with a significant improvement in disease free interval (DFI) and overall survival (OS)(P=0.001).ConclusionsCombined beta-glucan with IRE ablated PDA tumor cells elicited a potent trained response and augmented anti-tumor functionality at 12 months post IRE, which translated into an improved DFI and OS.Copyright © 2025 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.

10 keywords...

hide…