Salmonella flagella confer anti-tumor immunological effect via activating Flagellin/TLR5 signalling within tumor microenvironment  

作　　者：Jianxiang Chen Yiting Qiao Guo Chen Cunjie Chang Heng Dong Bo Tang Xiawei Cheng Xiufeng Liu Zichun Hua 

机构地区：[1]School of Life Sciences,Nanjing University,Nanjing 210023,China [2]Changzhou High-Tech Research Institute of Nanjing University and Jiangsu Target Pharma Laboratories Inc.,Changzhou 213164,China [3]College of Pharmacy,School of Medicine,Hangzhou Normal University,Hangzhou 311100,China [4]Department of Hepatology,the Affiliated Hospital of Hangzhou Normal University,Hangzhou Normal University,Hangzhou 310003,China [5]Division of Hepatobiliary and Pancreatic Surgery,Department of Surgery,the First Affiliated Hospital,School of Medicine,Zhejiang University [6]School of Biopharmacy,China Pharmaceutical University,Nanjing 211198,China

出　　处：《Acta Pharmaceutica Sinica B》2021年第10期3165-3177,共13页药学学报（英文版）

基　　金：supported by grants from the Jiangsu Provincial Nature Science Foundation(BK20192005,China);National Natural Science Foundation of China(81630092,81903143,81802338,and 82072646);Zhejiang Provincial Natural Science Foundation of China for Distinguished Young Scholars(LR21H160001);Start-up Grant of HZNU(4125C5021820470,China)。

摘　　要：Salmonella:mediated cancer therapy has achieved remarkable anti-tumor effects in experimental animal models,but the detailed mechanism remains unsolved.In this report,the active involvement of the host immune response in this process was confirmed by comparing the tumor-suppressive effects of Salmonella in immunocompetent and immunodeficient mice bearing melanoma allografts.Since flagella are key inducers of the host immune response during bacterial infection,flagella were genetically disrupted to analyse their involvement in Salmonella-mediated cancer therapy.The results showed that flagellum-deficient strains failed to induce significant anti-tumor effects,even when more bacteria were administered to offset the difference in invasion efficiency.Flagella mainly activate immune cells via Flagellin/Toll-like receptor 5(TLR5)signalling pathway.Indeed,we showed that exogenous activation of TLR5 signalling by recombinant Flagellin and exogenous expression of TLR5 both enhanced the therapeutic efficacy of flagellum-deficient Salmonella against melanoma.Our study highlighted the therapeutic value of the interaction between Salmonella and the host immune response through Flagellin/TLR5 signalling pathway during Salmonella-mediated cancer therapy,thereby suggesting the potential application of TLR5 agonists in the cancer immune therapy.

关 键 词：Bacteria-mediated cancer therapy SALMONELLA VNP20009 FLAGELLUM FLAGELLIN TLR5 NF-kB Cancer immune therapy 

分 类 号：R730.51[医药卫生—肿瘤]