S100a8/a9 regulated by <scp>LPS</scp>/<scp>TLR4</scp> axis plays an important role in <i>Salmonella</i>‐based tumor therapy and host defense
Bacteria are ideal anticancer agents and carriers due to their unique capabilities that are convenient in genetic manipulation, tumor-specific targeting, and deep-tissue penetration. However, the specific molecular mechanisms of bacteria-mediated cancer therapy (BMCT) have not been clarified. In this study, we found that TLR4 signaling pathway is critical for Salmonella-mediated tumor targeting, tumor suppression, and liver and spleen protection. TLR4 knockout in mice decreased the levels of cytokines and chemokines, such as S100a8, S100a9, TNF-α, and IL-1β, in tumor microenvironments (TMEs) after Salmonella treatment, which inhibited tumor cell death and nutrient release, led to reduced bacterial contents in tumors and attenuated antitumor efficacy in a negative feedback manner. Importantly, we found that S100a8 and S100a9 played a leading role in Salmonella-mediated cancer therapy (SMCT). The antitumor efficacy was abrogated and liver damage was prominent when blocked with a specific inhibitor. These findings elucidated the mechanism of Salmonella-mediated tumor targeting, suppression, and host antibacterial defense, providing insights into clinical cancer therapeutics.
Authors
- Wenzhi Tan (ORCID: https://orcid.org/0000-0003-0924-192X)
- Jin Zheng (ORCID: https://orcid.org/0000-0002-5005-9786)
- Zhen Xun (ORCID: https://orcid.org/0000-0002-4242-3402)
- Yujie Sun (ORCID: https://orcid.org/0009-0001-7178-1401)
- Jung‐Joon Min (ORCID: https://orcid.org/0000-0001-6358-2798)
- Xiaoqing Liu (ORCID: https://orcid.org/0000-0003-0982-4615)
- Mei Yang (ORCID: https://orcid.org/0000-0002-0062-605X)
- Jinling Liu (ORCID: https://orcid.org/0000-0003-1998-9739)
- Zhongying Li (ORCID: https://orcid.org/0000-0002-5130-3170)
- Yanxia Guo (ORCID: https://orcid.org/0009-0009-7522-4459)
- Chaohui Zuo (ORCID: https://orcid.org/0000-0002-1774-9259)
- Yu Chen (ORCID: https://orcid.org/0000-0001-9926-2518)
- Min Wen
Institutions
- Chonnam National University (KR)
- Central South University (CN)
- Hunan University (CN)
- Second Affiliated Hospital of Guangzhou Medical University (CN)
- Hunan Cancer Hospital (CN)
- Changsha University of Science and Technology (CN)
- South China University of Technology (CN)
- Guangzhou Medical University (CN)
Publication Details
- Journal
- International Journal of Cancer
- Published
- 2024-08-11
- DOI
- https://doi.org/10.1002/ijc.35128
- Citations
- 2
- Primary Topic
- Cancer Research and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.77
Funders
- National Natural Science Foundation of China
- National Research Foundation of Korea
- Natural Science Foundation of Hunan Province
- Fundamental Research Funds for the Central Universities