Irreversible Electroporation of Locally Advanced Pancreatic Cancer Transiently Alleviates Immune Suppression and Creates a Window for Antitumor T Cell Activation

Sunday, February 2, 2020

12:04 PM – 12:15 PM

Location: Galerie 1/2/3, 2nd Floor

Objective: 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=0.055).

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.

Author(s)

HS

Hester J. Scheffer, Dr.

MD, PhD
Amsterdam UMC - location VUmc

Disclosure: Disclosure information not submitted.
AS

Anita Stam, n/a

Msc
Amsterdam UMC

Disclosure: Disclosure information not submitted.

Presenting Author(s)

BG

Bart Geboers, Drs.

MD
Amsterdam UMC - location VUmc

Disclosure: Disclosure information not submitted.

Author(s)

LV

Laurien G.P.H. Vroomen, Drs.

MD
Amsterdam UMC - location VUmc

Disclosure: Disclosure information not submitted.
AR

Alette Ruarus, MD

Disclosure: Disclosure information not submitted.
Bd

Beaunelle de Bruijn, n/a

MSc
Amsterdam UMC

Disclosure: Disclosure information not submitted.
Pv

Petrousjka M.P. van den tol, Dr.

MD, PhD
Amsterdam UMC - location VUmc

Disclosure: Disclosure information not submitted.
GK

Geert Kazemier, n/a

MD, Phd
Amsterdam UMC

Disclosure: Disclosure information not submitted.
Martijn R. Meijerink, MD, PhD

Interventional Radiologist
Amsterdam UMC

Disclosure: Disclosure information not submitted.
Td

Tanja de Gruijl, n/a

Disclosure: Disclosure information not submitted.