title: The mannose-sensitive hemagglutination pilus strain of Pseudomonas aeruginosa shift peritoneal milky spot macrophages towards an M1 phenotype to dampen peritoneal dissemination.
abstract: Peritoneal dissemination (PD) of tumor cells is the most frequent pattern of gastric cancer recurrence and the leading cause of death. Peritoneal milky spots are deemed as the site of origin of gastric cancer PD wherein the main cellular components are macrophages. A vaccine derived from the mannose-sensitive hemagglutination pilus strain of Pseudomonas aeruginosa (PA-MSHA) has exhibit strong immune modulatory properties. In the present study, we tested the hypothesis whether the PA-MSHA vaccine activated peritoneal milky spot macrophages (PMSM) in a manner that would attenuate PD. It was observed that PA-MSHA activated PMSM towards a classical activation phenotype via a toll-like receptor4/9-dependent mechanism, which increased interleukin-12 levels and promoted the expression of co-stimulatory and antigen-presenting molecules like CD80, CD86, and MHC-II (P < 0.05). In addition, PA-MSHA-treated PMSM exhibited strong nonspecific antitumor effects in both contact-dependent and contact-independent modes of action (P < 0.05). In mice treated with PA-MSHA before inoculating gastric cancer cells, we noted alleviated PD toward the untreated mice. In conclusion, our findings demonstrated that PA-MSHA can stimulate PMSM towards an M1 phenotype and that activated PMSM inhibit gastric cancer growth and PD both in vitro and in vivo. The results of the current study provide a mechanistic insight that is relevant to the potential application of PA-MSHA in the treatment of gastric cancer-mediated PD.
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital of China Medical University, No.155 North Nanjing Street, Heping District, Shenyang, Liaoning Province, 110001, China.
authors.forename: Zhi-Feng
authors.initials: ZF
authors.lastname: Miao
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Zhao
authors.forename: Feng
authors.initials: F
authors.lastname: Miao
authors.forename: Zhen-Ning
authors.initials: ZN
authors.lastname: Wang
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Xu
authors.forename: Xiao-Yun
authors.initials: XY
authors.lastname: Mao
authors.forename: Jian
authors.initials: J
authors.lastname: Gao
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Wu
authors.forename: Xing-Yu
authors.initials: XY
authors.lastname: Liu
authors.forename: Yi
authors.initials: Y
authors.lastname: You
authors.forename: Hao
authors.initials: H
authors.lastname: Xu
authors.forename: Hui-Mian
authors.initials: HM
authors.lastname: Xu
mesh_terms: D000818:Animals; D001428:Bacterial Vaccines / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D006384:Hemagglutination; D007167:Immunotherapy; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D016328:NF-kappa B / Q000502:physiology; D010534:Peritoneal Neoplasms / Q000473:pathology / Q000628:therapy*; D010537:Peritoneum / Q000473:pathology*; D010641:Phenotype; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D013274:Stomach Neoplasms / Q000473:pathology*; D051197:Toll-Like Receptor 4 / Q000502:physiology; D051217:Toll-Like Receptor 9 / Q000502:physiology
chemical_list: D001428:Bacterial Vaccines; D016328:NF-kappa B; C495345:TLR4 protein, human; C495371:TLR9 protein, human; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9