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

作者机构：School of Life SciencesNanjing UniversityNanjing 210023China Changzhou High-Tech Research Institute of Nanjing University and Jiangsu Target Pharma Laboratories Inc.Changzhou 213164China College of PharmacySchool of MedicineHangzhou Normal UniversityHangzhou 311100China Department of Hepatologythe Affiliated Hospital of Hangzhou Normal UniversityHangzhou Normal UniversityHangzhou 310003China Division of Hepatobiliary and Pancreatic SurgeryDepartment of Surgerythe First Affiliated HospitalSchool of MedicineZhejiang University School of BiopharmacyChina Pharmaceutical UniversityNanjing 211198China 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2021年第11卷第10期

页      面：3165-3177页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

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) 

主　　题：Bacteria-mediated cancer therapy Salmonella VNP20009 Flagellum Flagellin TLR5 NF-kB Cancer immune therapy 

摘      要：Salmonella:mediated cancer therapy has achieved remarkable anti-tumor effects in experimental animal models,but the detailed mechanism remains *** 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 *** flagella are key inducers of the host immune response during bacterial infection,flagella were genetically disrupted to analyse their involvement in Salmonella-mediated cancer *** 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 *** mainly activate immune cells via Flagellin/Toll-like receptor 5(TLR5)signalling ***,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 *** 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.