Journal
NATURE COMMUNICATIONS
Volume 10, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-019-08782-1
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Funding
- Skip Viragh Foundation
- John S. Dunn Foundation
- MD Anderson Cancer Center/Emerson Collective Cancer Research Fund
- Gillson Longenbaugh Foundation
- Cancer Center Support Grant from the U.S. National Institutes of Health [P30CA016672]
- National Basic Research Program of China [2015CB931800]
- National Natural Science Foundation of China [81627901]
- China Anti-Cancer Association Chinese Fellowship [CF/16/431486]
- Foster Funding of the Fourth Hospital of Harbin Medical University [HYDSYPY201601]
- Union for International Cancer Control
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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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