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A toll-like receptor agonist mimicking microbial signal to generate tumor-suppressive macrophages
Yanxian Feng1; Ruoyu Mu1; Zhenzhen Wang2; Panfei Xing1; Junfeng Zhang2; Lei Dong2; Chunming Wang1
2019-05
Source PublicationNATURE COMMUNICATIONS
ISSN2041-1723
Abstract

Switching macrophages from a pro-tumor type to an anti-tumor state is a promising strategy for cancer immunotherapy. Existing agents, many derived from bacterial components, have safety or specificity concerns. Here, we postulate that the structures of the bacterial signals can be mimicked by using non-toxic biomolecules of simple design. Based on bioactivity screening, we devise a glucomannan polysaccharide with acetyl modification at a degree of 1.8 (acGM-1.8), which specifically activates toll-like receptor 2 (TLR2) signaling and consequently induces macrophages into an anti-tumor phenotype. For acGM-1.8, the degree of acetyl modification, glucomannan pattern, and acetylation-induced assembly are three crucial factors for its bioactivity. In mice, intratumoral injection of acGM-1.8 suppresses the growth of two tumor models, and this polysaccharide demonstrates higher safety than four classical TLR agonists. In summary, we report the design of a new, safe, and specific TLR2 agonist that can generate macrophages with strong anti-tumor potential in mice.

DOI10.1038/s41467-019-10354-2
Indexed BySCI
Language英语
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000468603900003
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Cited Times [WOS]:9   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorLei Dong
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau SAR, China
2.StateKey Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China
First Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Yanxian Feng,Ruoyu Mu,Zhenzhen Wang,et al. A toll-like receptor agonist mimicking microbial signal to generate tumor-suppressive macrophages[J]. NATURE COMMUNICATIONS,2019.
APA Yanxian Feng.,Ruoyu Mu.,Zhenzhen Wang.,Panfei Xing.,Junfeng Zhang.,...&Chunming Wang.(2019).A toll-like receptor agonist mimicking microbial signal to generate tumor-suppressive macrophages.NATURE COMMUNICATIONS.
MLA Yanxian Feng,et al."A toll-like receptor agonist mimicking microbial signal to generate tumor-suppressive macrophages".NATURE COMMUNICATIONS (2019).
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