1. Tissue Resistance Decrease during Irreversible Electroporation of Pancreatic Cancer as a Biomarker for the Adaptive Immune Response and Survival.
- Author
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Timmer FEF, Geboers B, Scheffer HJ, Bakker J, Ruarus AH, Dijkstra M, van der Lei S, Boon R, Nieuwenhuizen S, van den Bemd BAT, Schouten EAC, van den Tol PM, Puijk RS, de Vries JJJ, de Gruijl TD, and Meijerink MR
- Subjects
- Humans, Prospective Studies, Electroporation methods, Adaptive Immunity, Biomarkers, Pancreatic Neoplasms, Pancreatic Neoplasms therapy
- Abstract
Purpose: To correlate irreversible electroporation (IRE) procedural resistance changes with survival outcomes and the IRE-induced systemic immune response in patients with locally advanced pancreatic cancer (LAPC)., Materials and Methods: Data on IRE procedural tissue resistance (R) features and survival outcomes were collected from patients with LAPC treated within the context of 2 prospective clinical trials in a single tertiary center. Preprocedural and postprocedural peripheral blood samples were prospectively collected for immune monitoring. The change (ie, decrease) in R during the first 10 test pulses (ΔR
10p ) and during the total procedure (ΔRtotal ) were calculated. Patients were divided in 2 groups on the basis of the median change in R (large ΔR vs small ΔR) and compared for differences in overall survival (OS) and progression-free survival and immune cell subsets., Results: A total of 54 patients were included; of these, 20 underwent immune monitoring. Linear regression modeling showed that the first 10 test pulses reflected the change in tissue resistance during the total procedure appropriately (P < .001; R2 = 0.91). A large change in tissue resistance significantly correlated with a better OS (P = .026) and longer time to disease progression (P = .045). Furthermore, a large change in tissue resistance was associated with CD8+ T cell activation through significant upregulation of Ki-67+ (P = .02) and PD-1+ (P = .047). Additionally, this subgroup demonstrated significantly increased expression of CD80 on conventional dendritic cells (cDC1; P = .027) and PD-L1 on immunosuppressive myeloid-derived suppressor cells (P = .039)., Conclusions: IRE procedural resistance changes may serve as a biomarker for survival and IRE-induced systemic CD8+ T cell and cDC1 activation., (Copyright © 2023 SIR. Published by Elsevier Inc. All rights reserved.)- Published
- 2023
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