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Irreversible electroporation reverses resistance to immune checkpoint blockade in pancreatic cancer

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...

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Detalles Bibliográficos
Autores principales: Zhao, Jun, Wen, Xiaofei, Tian, Li, Li, Tingting, Xu, Chunyu, Wen, Xiaoxia, Melancon, Marites P., Gupta, Sanjay, Shen, Baozhong, Peng, Weiyi, Li, Chun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6385305/
https://www.ncbi.nlm.nih.gov/pubmed/30796212
http://dx.doi.org/10.1038/s41467-019-08782-1
Descripción
Sumario: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.