Tissue Resistance Decrease during Irreversible Electroporation of Pancreatic Cancer as a Biomarker for the Adaptive Immune Response and Survival

Purpose: To correlate irreversible electroporation (IRE) procedural resistance changes with survival outcomes and the IREinduced 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 (AR(10p)) and during the total procedure (ARtotal) were calculated. Patients were divided in 2 groups on the basis of the median change in R (large AR vs small AR) 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.