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Updated: Aug 6, 2026
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A Macrophage-Tumor Spheroid Co-Invasion Assay
Published on: January 24, 2025
Programmable-bacteria-macrophage backpacks for enhanced solid tumor therapy via mechanobiological interplay
Zhe Fan1, Pengfei Chen2, Shuangmei Zuo3
1Henan Institute of Advanced Technology, Zhengzhou University, Zhengzhou 450003, P.R. China; The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou 450052, P.R. China.
Cell Reports. Medicine
|July 17, 2026
Summary
Engineered bacteria activated by focused ultrasound (US) hyperthermia recruit immune cells by releasing CCL21. This approach enhances macrophage-mediated antitumor immunotherapy by remodeling the immunosuppressive tumor microenvironment (TME).
Area of Science:
- Biomedical Engineering
- Immunotherapy
- Cancer Research
Background:
- Adoptive cell-based immunotherapies face challenges against solid tumors due to tumor microenvironment (TME) immunosuppression and cellular changes.
- Existing treatments have limited efficacy in overcoming these obstacles.
Purpose of the Study:
- To develop a novel therapeutic system using engineered bacteria to overcome TME-mediated immunosuppression.
- To enhance the efficacy of adoptive cell-based immunotherapies against solid tumors.
Main Methods:
- Engineered bacteria with a temperature-actuated genetic switch for controlled CCL21 release.
- Focused ultrasound (US) hyperthermia to activate the genetic switch.
- Surface modification of bacteria for bromelain conjugation and macrophage 'backpack' formation.
- Intravenous administration of bacteria-loaded macrophages for targeted delivery.
Main Results:
- US-triggered activation promoted macrophage repolarization (CD86+) within the TME.
- Enhanced infiltration of immune cells, including dendritic cells and CD4+/CD8+ T cells.
- Reduced collagen I deposition and weakened tumor cell mechanobiological properties.
- Mitigation of tumor-induced immune evasion.
Conclusions:
- The engineered bacterial system effectively remodels the immunosuppressive TME.
- Macrophage-mediated delivery combined with US-triggered CCL21 release improves antitumor immunotherapy.
- This approach offers a promising strategy for enhancing solid tumor treatment.
