title: Dendritic cells stimulated with outer membrane protein A (OmpA) of Salmonella typhimurium generate effective anti-tumor immunity.
abstract: Gram-negative bacterial outer membrane proteins (Omps) have an important role in pathogenesis and signal reception. We previously reported that Acinetobacter OmpA (AbOmpA) induced maturation of bone marrow-derived dendritic cells (BMDCs) and that AbOmpA-primed DCs produced IL-12 which generated Th1 CD4(+) T-cells. We analyzed the effects of Salmonella typhimurium OmpA (OmpA-Sal) on dendritic cell (DC) maturation in the present study, and determined that tumor antigen-pulsed DCs stimulated with OmpA-Sal induced anti-tumor responses in a mouse model. OmpA-Sal activated BMDCs by augmenting expression of MHC class II and of the co-stimulatory molecules CD80 and CD86. RT-PCR revealed that IL-12(p40) gene expression is highly augmented in OmpA-Sal-stimulated BMDCs. DNA (CRT/E7) vaccination combined with OmpA-Sal stimulation generated more antigen-specific CD8(+) T-cells in the present study. Certain antigen-pulsed BMDCs stimulated with OmpA-Sal induced strong PADRE-specific CD4(+) and E7-specific CD8(+) T-cell responses. In addition, BMDCs stimulated with OmpA-Sal (OmpA-Sal-BMDCs) and pulsed with both E7 and PADRE peptide generated greater numbers of E7-specific CD8(+) effector and memory T-cells than those pulsed with E7 peptide alone. E7- and PADRE-expressing OmpA-Sal-BMDC vaccines resulted in significant long-term protective anti-tumor effects in vaccinated mice. Our data suggested that E7- and PADRE-expressing BMDCs that were matured in the presence of OmpA-Sal might enhance anti-tumor immunity and support the therapeutic use of OmpA-Sal in DC-based immunotherapy.
authors.affiliation: Department of Anatomy, Chung-Ang University College of Medicine, Dongjak-Gu, Seoul, Republic of Korea.
authors.forename: Min Ja
authors.initials: MJ
authors.lastname: Jang
authors.forename: Jee-Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Yoon Hee
authors.initials: YH
authors.lastname: Chung
authors.forename: Won Bok
authors.initials: WB
authors.lastname: Lee
authors.forename: Yong Kyoo
authors.initials: YK
authors.lastname: Shin
authors.forename: Jun Sik
authors.initials: JS
authors.lastname: Lee
authors.forename: Daejin
authors.initials: D
authors.lastname: Kim
authors.forename: Yeong-Min
authors.initials: YM
authors.lastname: Park
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D000954:Antigens, Surface / Q000032:analysis; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000737:chemistry / Q000276:immunology*; D005260:Female; D020869:Gene Expression Profiling; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012486:Salmonella typhimurium / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D019496:Cancer Vaccines; D016207:Cytokines; C078167:OMPA outer membrane proteins