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Irreversible electroporation of locally advanced pancreatic cancer transiently alleviates immune suppression and creates a window for antitumor T cell activation
OncoImmunology  (IF8.11),  Pub Date : 2019-08-28, DOI: 10.1080/2162402x.2019.1652532
Hester J. Scheffer,Anita G.M. Stam,Bart Geboers,Laurien G.P.H. Vroomen,Alette Ruarus,Beaunelle de Bruijn,M. Petrousjka van den Tol,Geert Kazemier,Martijn R. Meijerink,Tanja D. de Gruijl

ABSTRACT

Purpose: Local tumor ablation through irreversible electroporation (IRE) may offer a novel therapeutic option for locally advanced pancreatic cancer (LAPC). It may also serve as a means of in vivo vaccination. To obtain evidence of the induction of systemic antitumor immunity following local IRE-mediated ablation, we performed an explorative immune monitoring study. Methods: In ten patients enrolled in a clinical trial exploring the safety, feasibility, and efficacy of percutaneous image-guided IRE in LAPC, we determined the frequency and activation state of lymphocytic and myeloid subsets in pre- and post-treatment peripheral blood samples using flow cytometry. Tumor-specific systemic T cell responses to the pancreatic cancer associated antigen Wilms Tumor (WT)1 were determined after in vitro stimulation in an interferon-y enzyme-linked immunospot assay (Elispot), at baseline and at 2 weeks and 3 months after IRE. Results: Our data showed a transient decrease in systemic regulatory T cells (Treg) and a simultaneous transient increase in activated PD-1+ T cells, consistent with the temporary reduction of tumor-related immune suppression after the IRE procedure. Accordingly, we found post-IRE boosting of a pre-existing WT1 specific T cell response in two out of three patients as well as the de novo induction of these responses in another two patients. There was a trend for these WT1 T cell responses to be related to longer overall survival (p = .055). Conclusions: These findings are consistent with a systemic and tumor-specific immune stimulatory effect of IRE and support the combination of percutaneous IRE with therapeutic immune modulation.