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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, recruit immune cells to solid tumors. This novel approach reprograms macrophages, enhancing T cell infiltration and improving cancer immunotherapy efficacy.
Area of Science:
- Biomedical Engineering
- Cancer Immunology
- Microbiology
Background:
- Adoptive cell-based immunotherapies face challenges in solid tumors due to tumor microenvironment (TME) and cellular changes.
- Current treatments exhibit limited efficacy against solid tumors.
Purpose of the Study:
- To engineer a novel therapeutic bacterial system for enhanced solid tumor immunotherapy.
- To overcome TME-induced immunosuppression and improve immune cell infiltration.
Main Methods:
- Engineered bacteria with a temperature-actuated genetic switch for controlled therapeutic release.
- Focused ultrasound (US) hyperthermia to activate the genetic switch and trigger CCL21 release.
- Surface modification of bacteria for bromelain conjugation and macrophage 'backpack' formation for targeted delivery.
Main Results:
- US activation promoted macrophage repolarization (CD86+) and enhanced immune cell infiltration within the TME.
- Treatment reduced collagen I deposition and weakened tumor cell mechanobiological properties.
- Systemic immune evasion was mitigated, leading to improved antitumor responses.
Conclusions:
- The engineered bacterial system effectively remodels the immunosuppressive TME via macrophage-mediated delivery and US-triggered CCL21 release.
- This approach facilitates dendritic cell and CD4+/CD8+ T cell infiltration, significantly improving antitumor immunotherapy outcomes.
