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Interventional hydrogel microsphere vaccine as an immune amplifier for activated antitumour immunity after ablation therapy

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  • Xiaoyu Liu

    (Ruijin Hospital, Shanghai Jiao Tong University School of Medicine)

  • Yaping Zhuang

    (Ruijin Hospital, Shanghai Jiao Tong University School of Medicine)

  • Wei Huang

    (Ruijin Hospital, Shanghai Jiao Tong University School of Medicine)

  • Zhuozhuo Wu

    (Ruijin Hospital, Shanghai Jiao Tong University School of Medicine)

  • Yingjie Chen

    (Ruijin Hospital, Shanghai Jiao Tong University School of Medicine)

  • Qungang Shan

    (Ruijin Hospital, Shanghai Jiao Tong University School of Medicine)

  • Yuefang Zhang

    (Institute of Neuroscience, CAS Key Laboratory of Primate Neurobiology, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology)

  • Zhiyuan Wu

    (Ruijin Hospital, Shanghai Jiao Tong University School of Medicine)

  • Xiaoyi Ding

    (Ruijin Hospital, Shanghai Jiao Tong University School of Medicine)

  • Zilong Qiu

    (Institute of Neuroscience, CAS Key Laboratory of Primate Neurobiology, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology)

  • Wenguo Cui

    (Ruijin Hospital, Shanghai Jiao Tong University School of Medicine)

  • Zhongmin Wang

    (Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
    Ruijin Hospital Luwan Branch, Shanghai Jiao Tong University School of Medicine)

Abstract

The response rate of pancreatic cancer to chemotherapy or immunotherapy pancreatic cancer is low. Although minimally invasive irreversible electroporation (IRE) ablation is a promising option for irresectable pancreatic cancers, the immunosuppressive tumour microenvironment that characterizes this tumour type enables tumour recurrence. Thus, strengthening endogenous adaptive antitumour immunity is critical for improving the outcome of ablation therapy and post-ablation immune therapy. Here we present a hydrogel microsphere vaccine that amplifies post-ablation anti-cancer immune response via releasing its cargo of FLT3L and CD40L at the relatively lower pH of the tumour bed. The vaccine facilitates migration of the tumour-resident type 1 conventional dendritic cells (cDC1) to the tumour-draining lymph nodes (TdLN), thus initiating the cDC1-mediated antigen cross-presentation cascade, resulting in enhanced endogenous CD8+ T cell response. We show in an orthotopic pancreatic cancer model in male mice that the hydrogel microsphere vaccine transforms the immunologically cold tumour microenvironment into hot in a safe and efficient manner, thus significantly increasing survival and inhibiting the growth of distant metastases.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39759-w
    DOI: 10.1038/s41467-023-39759-w
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    References listed on IDEAS

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    1. 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.
    2. Irene Ischenko & Stephen D’Amico & Manisha Rao & Jinyu Li & Michael J. Hayman & Scott Powers & Oleksi Petrenko & Nancy C. Reich, 2021. "KRAS drives immune evasion in a genetic model of pancreatic cancer," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    3. Keisuke Yamamoto & Anthony Venida & Julian Yano & Douglas E. Biancur & Miwako Kakiuchi & Suprit Gupta & Albert S. W. Sohn & Subhadip Mukhopadhyay & Elaine Y. Lin & Seth J. Parker & Robert S. Banh & Jo, 2020. "Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I," Nature, Nature, vol. 581(7806), pages 100-105, May.
    4. Brandon J. Burbach & Stephen D. O’Flanagan & Qi Shao & Katharine M. Young & Joseph R. Slaughter & Meagan R. Rollins & Tami Jo L. Street & Victoria E. Granger & Lalit. K. Beura & Samira M. Azarin & Sat, 2021. "Irreversible electroporation augments checkpoint immunotherapy in prostate cancer and promotes tumor antigen-specific tissue-resident memory CD8+ T cells," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
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