Thermal-responsive activation of engineered bacteria to trigger antitumor immunity post microwave ablation therapy
Abstract Incomplete tumor removal after microwave ablation (MWA), a widely used hyperthermia-based therapy, can result in tumor recurrence. Herein, attenuated Salmonella typhimurium VNP20009 is engineered to release interleukin-15&interleukin-15-receptor-alpha (IL-15&IL-15Rα) in response to...
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| Format: | Article |
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Nature Portfolio
2024-12-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54883-x |
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| author | Yumin Wu Bo Liu Yifan Yan Chuntao Gong Kaiwei Wang Nanhui Liu Yujie Zhu Maoyi Li Chunjie Wang Yizhe Yang Liangzhu Feng Zhuang Liu |
| author_facet | Yumin Wu Bo Liu Yifan Yan Chuntao Gong Kaiwei Wang Nanhui Liu Yujie Zhu Maoyi Li Chunjie Wang Yizhe Yang Liangzhu Feng Zhuang Liu |
| author_sort | Yumin Wu |
| collection | DOAJ |
| description | Abstract Incomplete tumor removal after microwave ablation (MWA), a widely used hyperthermia-based therapy, can result in tumor recurrence. Herein, attenuated Salmonella typhimurium VNP20009 is engineered to release interleukin-15&interleukin-15-receptor-alpha (IL-15&IL-15Rα) in response to mildly elevated temperature. Such 15&15R@VNP colonizes in tumors upon intravenous injection, and the expression of IL-15&IL-15Rα is triggered by MWA. Anti-tumor immune responses are elicited, efficiently suppressing tumor growth even after incomplete microwave ablation. We further design VNP20009 with thermal-responsive co-expression of both IL-15&IL-15Rα and soluble programmed cell death protein (sPD-1). Such sPD-1-15&15R@VNP can also reverse the functional suppression of immune cells driven by PD-1/PD-L1 axis, reinvigorating progenitor exhausted T cells, a critical subset of cytotoxic T lymphocytes responsive to immune checkpoint blockade. Such thermal-responsive engineered bacteria are thus a promising adjuvant therapy to potentiate tumor ablation therapies via effectively activating antitumor immunity. |
| format | Article |
| id | doaj-art-28603dcb87284fb39d14fb9d5a4bd6a5 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-28603dcb87284fb39d14fb9d5a4bd6a52025-08-20T02:20:41ZengNature PortfolioNature Communications2041-17232024-12-0115111910.1038/s41467-024-54883-xThermal-responsive activation of engineered bacteria to trigger antitumor immunity post microwave ablation therapyYumin Wu0Bo Liu1Yifan Yan2Chuntao Gong3Kaiwei Wang4Nanhui Liu5Yujie Zhu6Maoyi Li7Chunjie Wang8Yizhe Yang9Liangzhu Feng10Zhuang Liu11Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Institute of Functional Nano & Soft Materials (FUNSOM), Soochow UniversityJiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Institute of Functional Nano & Soft Materials (FUNSOM), Soochow UniversityJiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Institute of Functional Nano & Soft Materials (FUNSOM), Soochow UniversityInnoBM PharmaceuticalsCollege of Pharmaceutical Sciences, Soochow UniversityJiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Institute of Functional Nano & Soft Materials (FUNSOM), Soochow UniversityJiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Institute of Functional Nano & Soft Materials (FUNSOM), Soochow UniversityJiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Institute of Functional Nano & Soft Materials (FUNSOM), Soochow UniversityJiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Institute of Functional Nano & Soft Materials (FUNSOM), Soochow UniversityJiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Institute of Functional Nano & Soft Materials (FUNSOM), Soochow UniversityJiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Institute of Functional Nano & Soft Materials (FUNSOM), Soochow UniversityJiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Institute of Functional Nano & Soft Materials (FUNSOM), Soochow UniversityAbstract Incomplete tumor removal after microwave ablation (MWA), a widely used hyperthermia-based therapy, can result in tumor recurrence. Herein, attenuated Salmonella typhimurium VNP20009 is engineered to release interleukin-15&interleukin-15-receptor-alpha (IL-15&IL-15Rα) in response to mildly elevated temperature. Such 15&15R@VNP colonizes in tumors upon intravenous injection, and the expression of IL-15&IL-15Rα is triggered by MWA. Anti-tumor immune responses are elicited, efficiently suppressing tumor growth even after incomplete microwave ablation. We further design VNP20009 with thermal-responsive co-expression of both IL-15&IL-15Rα and soluble programmed cell death protein (sPD-1). Such sPD-1-15&15R@VNP can also reverse the functional suppression of immune cells driven by PD-1/PD-L1 axis, reinvigorating progenitor exhausted T cells, a critical subset of cytotoxic T lymphocytes responsive to immune checkpoint blockade. Such thermal-responsive engineered bacteria are thus a promising adjuvant therapy to potentiate tumor ablation therapies via effectively activating antitumor immunity.https://doi.org/10.1038/s41467-024-54883-x |
| spellingShingle | Yumin Wu Bo Liu Yifan Yan Chuntao Gong Kaiwei Wang Nanhui Liu Yujie Zhu Maoyi Li Chunjie Wang Yizhe Yang Liangzhu Feng Zhuang Liu Thermal-responsive activation of engineered bacteria to trigger antitumor immunity post microwave ablation therapy Nature Communications |
| title | Thermal-responsive activation of engineered bacteria to trigger antitumor immunity post microwave ablation therapy |
| title_full | Thermal-responsive activation of engineered bacteria to trigger antitumor immunity post microwave ablation therapy |
| title_fullStr | Thermal-responsive activation of engineered bacteria to trigger antitumor immunity post microwave ablation therapy |
| title_full_unstemmed | Thermal-responsive activation of engineered bacteria to trigger antitumor immunity post microwave ablation therapy |
| title_short | Thermal-responsive activation of engineered bacteria to trigger antitumor immunity post microwave ablation therapy |
| title_sort | thermal responsive activation of engineered bacteria to trigger antitumor immunity post microwave ablation therapy |
| url | https://doi.org/10.1038/s41467-024-54883-x |
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