ORIGINAL RESEARCH article
Front. Immunol.
Sec. Microbial Immunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1637667
Targeting the LPS-STING axis: Neomycin restores STING-mediated anti-tumor immune suppression and inhibits tumor growth
Provisionally accepted
- 1Renmin Hospital of Wuhan University, Wuhan, China
- 2Wuhan University State Key Laboratory of Virology, Wuhan, China
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The interplay between microbial metabolites and host immunity within the tumor microenvironment (TME) critically modulates anti-tumor immune responses. In this context, the role of Gram-negative bacteria and their cell wall component lipopolysaccharide (LPS) in tumor progression warrants further investigation. This study demonstrated that low-dose LPS pretreatment significantly suppressed type I interferon (IFN-β) secretion by macrophages upon stimulation with tumor cell debris. This phenomenon was directly linked to LPS-mediated immunosuppression, indicating that elevated LPS levels in the TME inhibit anti-tumor innate immunity by impairing macrophage function. Mechanistically, LPS disrupted endogenous signaling pathways in macrophages, blunting their ability to sense tumor-derived damage signals and thereby impairing innate immune cell-mediated tumor clearance. To counteract this effect, melanoma-bearing mice were treated with neomycin, an aminoglycoside antibiotic that reduces LPS-producing bacteria. Neomycin treatment markedly inhibited melanoma growth and synergized with STING agonists, suggesting a potential strategy to enhance tumor immunotherapy by combining LPS modulation with innate immune activation.
Keywords: microbiome, lipopolysaccharide, TBK1, tumor, Neomycin
Received: 29 May 2025; Accepted: 17 Oct 2025.
Copyright: © 2025 HONG, Fu, Tian, Li, Liu, Ye, Wu and Zhu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Chengliang Zhu, zhuchengliang@whu.edu.cn
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