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A Syngeneic Pancreatic Cancer Mouse Model to Study the Effects of Irreversible Electroporation
08:05

A Syngeneic Pancreatic Cancer Mouse Model to Study the Effects of Irreversible Electroporation

Published on: June 8, 2018

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Irreversible electroporation reverses resistance to immune checkpoint blockade in pancreatic cancer

Jun Zhao1, Xiaofei Wen1,2,3, Li Tian4

  • 1Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, 77054, USA.

Nature Communications
|February 24, 2019
PubMed

Immunotherapy has only limited efficacy against pancreatic ductal adenocarcinoma (PDAC) due to the presence of an immunosuppressive tumor-associated stroma. Here, we demonstrate an effective modulation of that stroma by irreversible electroporation (IRE), a local ablation technique that has received regulatory approval in the United States. IRE induces immunogenic cell death, activates dendritic cells, and alleviates stroma-induced immunosuppression without depleting tumor-restraining collagen. The combination of IRE and anti-programmed cell death protein 1 (anti-PD1) immune checkpoint blockade promotes selective tumor infiltration by CD8+ T cells and significantly prolongs survival in a murine orthotopic PDAC model with a long-term memory immune response. Our results suggest that IRE is a promising approach to potentiate the efficacy of immune checkpoint blockade in PDAC.

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