Irreversible electroporation reverses resistance to immune checkpoint blockade in pancreatic cancer

Jun Zhao, Xiaofei Wen, Li Tian, Tingting Li, Chunyu Xu, Xiaoxia Wen, Marites P. Melancon, Sanjay Gupta, Baozhong Shen, Weiyi Peng and Chun Li ()
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Jun Zhao: The University of Texas MD Anderson Cancer Center
Xiaofei Wen: The University of Texas MD Anderson Cancer Center
Li Tian: The University of Texas MD Anderson Cancer Center
Tingting Li: The University of Texas MD Anderson Cancer Center
Chunyu Xu: The University of Texas MD Anderson Cancer Center
Xiaoxia Wen: The University of Texas MD Anderson Cancer Center
Marites P. Melancon: The University of Texas MD Anderson Cancer Center
Sanjay Gupta: The University of Texas MD Anderson Cancer Center
Baozhong Shen: Molecular Imaging Research Center of Harbin Medical University
Weiyi Peng: The University of Texas MD Anderson Cancer Center
Chun Li: The University of Texas MD Anderson Cancer Center

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-08782-1

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