title: Pseudomonas aeruginosa mannose-sensitive hemagglutinin promotes T-cell response via toll-like receptor 4-mediated dendritic cells to slow tumor progression in mice.
abstract: Pseudomonas aeruginosa-mannose-sensitive hemagglutinin (PA-MSHA) as a drug may kill tumor cells and has been used clinically. However, the antitumor immune response of PA-MSHA is not completely understood. In this study, we found that treating Lewis lung carcinoma (3LL)-bearing mice with PA-MSHA plus 3LL antigen led to slower tumor progression and longer survival. After PA-MSHA treatment, T-cell number and dendritic cell maturation were both increased significantly at the tumor site. In addition, PA-MSHA in vitro stimulation resulted in the maturation of bone marrow-derived dendritic cells (BMDCs) from naive mice, showing higher costimulatory molecule expression, more cytokine secretion, lower endocytic activity, and stronger capacity to enhance T-cell activation. Toll-like receptor (TLR)4 but not TLR2 was required in the maturation process. More importantly, PA-MSHA-induced DCs were essential for PA-MSHA to enhance activation, expansion, and interferon (IFN)-γ secretion of TLR4-mediated T cells, which play a role in the antitumor effect of PA-MSHA. Thus, this study reveals PA-MSHA as a novel TLR4 agonist that elicits antitumor immune response to slow tumor progression.
authors.affiliation: Key Laboratory of Medical Molecular Virology of MOE/MOH, Department of Immunology, School of Basic Medical Sciences and Biotherapy Research Center (M.Z., F.L., Y.Z., L.W., W.L., Y.C.) and Department of General Surgery, Zhongshan Hospital (M.Y.), Fudan University, Shanghai, China; and Beijing Wanter Biopharmaceutical Co., Ltd., Huairou Yanqi Economic-Technical Development Area, Beijing, China (D.H., X.W.).
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Feifei
authors.initials: F
authors.lastname: Luo
authors.forename: Yufei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Luman
authors.initials: L
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Lin
authors.forename: Mengxuan
authors.initials: M
authors.lastname: Yang
authors.forename: Dali
authors.initials: D
authors.lastname: Hu
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Wu
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Chu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000276:immunology / Q000494:pharmacology*; D018827:Carcinoma, Lewis Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D005260:Female; D006388:Hemagglutinins / Q000276:immunology / Q000494:pharmacology*; D008358:Mannose / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D011550:Pseudomonas aeruginosa / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D006388:Hemagglutinins; D051197:Toll-Like Receptor 4; D008358:Mannose