Irreversible electroporation reverses resistance to immune checkpoint blockade in pancreatic cancer

Jun Zhao(The University of Texas MD Anderson Cancer Center), Xiaofei Wen(The University of Texas MD Anderson Cancer Center), Tian Li(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(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
February 22, 2019
10.1038/s41467-019-08782-1
Cited by 265Open Access
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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.

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