Irreversible electroporation reverses resistance to immune checkpoint blockade in pancreatic cancer.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30796212.
- Also identified by DOI 10.1038/s41467-019-08782-1 and PMC identifier 6385305.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sup>+</sup> 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.
Medical subject headings
- CD8-Positive T-Lymphocytes
- Carcinoma, Pancreatic Ductal
- Electroporation
- Immunotherapy
- Melanoma, Experimental
- Pancreatic Neoplasms