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Irreversible electroporation reverses resistance to immune checkpoint blockade in pancreatic cancer

Author

Listed:
  • Jun Zhao

    (The University of Texas MD Anderson Cancer Center)

  • Xiaofei Wen

    (The University of Texas MD Anderson Cancer Center
    Molecular Imaging Research Center of Harbin Medical University
    Fourth Hospital of Harbin Medical University)

  • Li Tian

    (The University of Texas MD Anderson Cancer Center)

  • Tingting Li

    (The University of Texas MD Anderson Cancer Center
    University of Electronic Science and Technology of China)

  • 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

    (Molecular Imaging Research Center of Harbin Medical University
    Fourth Hospital of Harbin Medical University)

  • Weiyi Peng

    (The University of Texas MD Anderson Cancer Center)

  • Chun Li

    (The University of Texas MD Anderson Cancer Center)

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.

Suggested Citation

  • Jun Zhao & Xiaofei Wen & Li Tian & Tingting Li & Chunyu Xu & Xiaoxia Wen & Marites P. Melancon & Sanjay Gupta & Baozhong Shen & Weiyi Peng & Chun Li, 2019. "Irreversible electroporation reverses resistance to immune checkpoint blockade in pancreatic cancer," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08782-1
    DOI: 10.1038/s41467-019-08782-1
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    Cited by:

    1. Zi-Yi Han & Zhuang-Jiong Fu & Yu-Zhang Wang & Cheng Zhang & Qi-Wen Chen & Jia-Xin An & Xian-Zheng Zhang, 2024. "Probiotics functionalized with a gallium-polyphenol network modulate the intratumor microbiota and promote anti-tumor immune responses in pancreatic cancer," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    2. Xiaoyu Liu & Yaping Zhuang & Wei Huang & Zhuozhuo Wu & Yingjie Chen & Qungang Shan & Yuefang Zhang & Zhiyuan Wu & Xiaoyi Ding & Zilong Qiu & Wenguo Cui & Zhongmin Wang, 2023. "Interventional hydrogel microsphere vaccine as an immune amplifier for activated antitumour immunity after ablation therapy," Nature Communications, Nature, vol. 14(1), pages 1-19, December.

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