title: Enhanced activation of human dendritic cells by silencing SOCS1 and activating TLRs simultaneously.
abstract: There was established evidence that silencing the attenuator and activating the TLRs could activate the dendritic cells in synergic effects. In this study, we constructed a plasmid, namely pshS1NH, which encodes SOCS1-shRNA, NY-ESO-1-MAGE3 (HLA-A2*0201) fusion antigen and secretory HMGB1, an agent used to modify dendritic cells (DCs), aiming to generate potent DC vaccine against tumors. The SOCS1-shRNA could efficiently downregulate the expression of SOCS1, as indicated by real-time RT-PCR and Western blot. The fusion antigen was detected in the pshS1NH-DCs by PCR and Western blot. Simultaneously, HMGB1 level in the pshS1NH-DCs culture media was significantly higher than that in the control DCs culture media. Levels of Th1 cytokines in pshS1NH-DCs culture media, such as IL-1β, IL-6, TNF-α and IL-12p70, were dramatically higher than those in control DCs culture media. In addition, lymphocytes co-cultured with pshS1NH-DCs secreted dramatically higher level of IFN-γ, whereas no difference was detected in IL-4 levels. Taken together, these data suggest that pshS1NH-DCs may be a potential adjuvant immunotherapy for cancers in clinical applications.
authors.affiliation: Department of Biotherapy, Tianjin Medical University Cancer Institute and Hospital, Huanhuxi Road, Hexi District, Tianjin 300060, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Jinpu
authors.initials: J
authors.lastname: Yu
authors.forename: Lili
authors.initials: L
authors.lastname: Yang
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Feng
authors.initials: F
authors.lastname: Wei
authors.forename: Hua
authors.initials: H
authors.lastname: Zhao
authors.forename: Wenwen
authors.initials: W
authors.lastname: Yu
authors.forename: Xiubao
authors.initials: X
authors.lastname: Ren
mesh_terms: D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D020868:Gene Silencing; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology; D006609:High Mobility Group Proteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D009369:Neoplasms / Q000628:therapy*; D010957:Plasmids / Q000235:genetics / Q000627:therapeutic use*; D034741:RNA, Small Interfering / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology*
chemical_list: D016207:Cytokines; C486328:HBP1 protein, human; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D006609:High Mobility Group Proteins; D034741:RNA, Small Interfering; D012097:Repressor Proteins; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D051193:Toll-Like Receptors