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Stimulation of tumoricidal immunity via bacteriotherapy inhibits glioblastoma relapse

Author

Listed:
  • Yulin Zhang

    (Shandong University
    Shandong University
    Shandong University)

  • Kaiyan Xi

    (Shandong University
    Shandong University
    Shandong University)

  • Zhipeng Fu

    (Shandong University)

  • Yuying Zhang

    (Shandong University)

  • Bo Cheng

    (Qilu Hospital affiliated to Shandong University)

  • Fan Feng

    (Shandong University
    Shandong University)

  • Yuanmin Dong

    (Shandong University)

  • Zezheng Fang

    (Shandong University
    Shandong University)

  • Yi Zhang

    (Shandong University
    Shandong University)

  • Jianyu Shen

    (Shandong University
    Shandong University)

  • Mingrui Wang

    (Shandong University
    Shandong University)

  • Xu Han

    (Shandong University
    Shandong University)

  • Huimin Geng

    (Shandong University
    Shandong University)

  • Lei Sun

    (Shandong University)

  • Xingang Li

    (Shandong University
    Jinan Microecological Biomedicine Shandong Laboratory
    Shandong Key Laboratory of Brain Function Remodeling)

  • Chen Chen

    (Shandong University)

  • Xinyi Jiang

    (Shandong University)

  • Shilei Ni

    (Shandong University
    Shandong University)

Abstract

Glioblastoma multiforme (GBM) is a highly aggressive brain tumor characterized by invasive behavior and a compromised immune response, presenting treatment challenges. Surgical debulking of GBM fails to address its highly infiltrative nature, leaving neoplastic satellites in an environment characterized by impaired immune surveillance, ultimately paving the way for tumor recurrence. Tracking and eradicating residual GBM cells by boosting antitumor immunity is critical for preventing postoperative relapse, but effective immunotherapeutic strategies remain elusive. Here, we report a cavity-injectable bacterium-hydrogel superstructure that targets GBM satellites around the cavity, triggers GBM pyroptosis, and initiates innate and adaptive immune responses, which prevent postoperative GBM relapse in male mice. The immunostimulatory Salmonella delivery vehicles (SDVs) engineered from attenuated Salmonella typhimurium (VNP20009) seek and attack GBM cells. Salmonella lysis-inducing nanocapsules (SLINs), designed to trigger autolysis, are tethered to the SDVs, eliciting antitumor immune response through the intracellular release of bacterial components. Furthermore, SDVs and SLINs administration via intracavitary injection of the ATP-responsive hydrogel can recruit phagocytes and promote antigen presentation, initiating an adaptive immune response. Therefore, our work offers a local bacteriotherapy for stimulating anti-GBM immunity, with potential applicability for patients facing malignancies at a high risk of recurrence.

Suggested Citation

  • Yulin Zhang & Kaiyan Xi & Zhipeng Fu & Yuying Zhang & Bo Cheng & Fan Feng & Yuanmin Dong & Zezheng Fang & Yi Zhang & Jianyu Shen & Mingrui Wang & Xu Han & Huimin Geng & Lei Sun & Xingang Li & Chen Che, 2024. "Stimulation of tumoricidal immunity via bacteriotherapy inhibits glioblastoma relapse," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48606-5
    DOI: 10.1038/s41467-024-48606-5
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    References listed on IDEAS

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