Stimulation of tumoricidal immunity via bacteriotherapy inhibits glioblastoma relapse

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 Chen (), Xinyi Jiang () and Shilei Ni ()
Additional contact information
Yulin Zhang: Shandong University
Kaiyan Xi: Shandong University
Zhipeng Fu: Shandong University
Yuying Zhang: Shandong University
Bo Cheng: Qilu Hospital affiliated to Shandong University
Fan Feng: Shandong University
Yuanmin Dong: Shandong University
Zezheng Fang: Shandong University
Yi Zhang: Shandong University
Jianyu Shen: Shandong University
Mingrui Wang: Shandong University
Xu Han: Shandong University
Huimin Geng: Shandong University
Lei Sun: Shandong University
Xingang Li: Shandong University
Chen Chen: Shandong University
Xinyi Jiang: Shandong University
Shilei Ni: Shandong University

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-48606-5

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