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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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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 |
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author | Zhao, Jun Wen, Xiaofei Tian, Li Li, Tingting Xu, Chunyu Wen, Xiaoxia Melancon, Marites P. Gupta, Sanjay Shen, Baozhong Peng, Weiyi Li, Chun |
author_facet | Zhao, Jun Wen, Xiaofei Tian, Li Li, Tingting Xu, Chunyu Wen, Xiaoxia Melancon, Marites P. Gupta, Sanjay Shen, Baozhong Peng, Weiyi Li, Chun |
author_sort | Zhao, Jun |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6385305 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-63853052019-02-25 Irreversible electroporation reverses resistance to immune checkpoint blockade in pancreatic cancer Zhao, Jun Wen, Xiaofei Tian, Li Li, Tingting Xu, Chunyu Wen, Xiaoxia Melancon, Marites P. Gupta, Sanjay Shen, Baozhong Peng, Weiyi Li, Chun Nat Commun Article 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. Nature Publishing Group UK 2019-02-22 /pmc/articles/PMC6385305/ /pubmed/30796212 http://dx.doi.org/10.1038/s41467-019-08782-1 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Zhao, Jun Wen, Xiaofei Tian, Li Li, Tingting Xu, Chunyu Wen, Xiaoxia Melancon, Marites P. Gupta, Sanjay Shen, Baozhong Peng, Weiyi Li, Chun Irreversible electroporation reverses resistance to immune checkpoint blockade in pancreatic cancer |
title | Irreversible electroporation reverses resistance to immune checkpoint blockade in pancreatic cancer |
title_full | Irreversible electroporation reverses resistance to immune checkpoint blockade in pancreatic cancer |
title_fullStr | Irreversible electroporation reverses resistance to immune checkpoint blockade in pancreatic cancer |
title_full_unstemmed | Irreversible electroporation reverses resistance to immune checkpoint blockade in pancreatic cancer |
title_short | Irreversible electroporation reverses resistance to immune checkpoint blockade in pancreatic cancer |
title_sort | irreversible electroporation reverses resistance to immune checkpoint blockade in pancreatic cancer |
topic | Article |
url | 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 |
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