title: Addition of CpG ODN and Poly (I:C) to a standard maturation cocktail generates monocyte-derived dendritic cells and induces a potent Th1 polarization with migratory capacity.
abstract: Monocyte-derived dendritic cells (DCs) are used as immunoadjuvant cells in cancer vaccines and have made great progress. However, an optimal DCs subset is vital for this treatment effect, the current 'gold standard' cytokine cocktail DCs have a shortcoming in their cytokines secretion, especially IL-12p70, mainly because of the existence of PGE2. Therefore, it is necessary to find an appropriate DCs-based immunotherapeutic protocol. In this study, we compared a novel 'improved' maturation cytokine cocktail with the current 'gold standard' maturation cytokine cocktail used for generating standard DCs. The 'improved' maturation cytokine cocktail DCs showed a higher levels surface markers expression (CD80, CD83, CD86 and HLA-DR), the chemokine receptors CXCR4 and CCR7 and chemokine CCL19, CCL21 and CXCL21, whereas CCR5 expression was reduced. Most importantly, in contrast to 'gold standard' DCs, which secrete little IL-12p70 and as a result induce mainly Th2 immunity, 'improved' cytokine cocktail DCs secreted higher levels IL-12p70 and also secreted similar concentration IL-10. To removal of PGE2 from the 'improved' DCs did increase the IL-12p70 production. In conclusion, we here present the 'improved' DCs, as an optimal maturation cocktail protocol, can induce high migratory potential, generate immunostimulatory DCs, produce higher levels IL-12p70 with superior capacity to induce Th1 immunity, when compared with the 'gold standard' DCs.
authors.affiliation: a Department of Laboratory Medicine ; Affiliated Provincial Hospital of Anhui Medical University ; Hefei , Anhui , China.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhu
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Hong
authors.initials: H
authors.lastname: Su
authors.forename: Qiong
authors.initials: Q
authors.lastname: Huang
authors.forename: Baolong
authors.initials: B
authors.lastname: Wang
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology; D018122:B7-1 Antigen / Q000032:analysis; D051940:B7-2 Antigen / Q000032:analysis; D019496:Cancer Vaccines / Q000276:immunology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002465:Cell Movement; D054415:Chemokine CCL19 / Q000032:analysis; D054421:Chemokine CCL21 / Q000032:analysis; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D015232:Dinoprostone / Q000494:pharmacology; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000276:immunology*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D011070:Poly I-C / Q000494:pharmacology*; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology* / Q000502:physiology
chemical_list: D000954:Antigens, Surface; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C515460:CCL19 protein, human; C515478:CCL21 protein, human; C408982:CPG-oligonucleotide; D019496:Cancer Vaccines; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D016207:Cytokines; C508609:IL10 protein, human; D009838:Oligodeoxyribonucleotides; D019707:Receptors, Chemokine; D016753:Interleukin-10; D018664:Interleukin-12; D015232:Dinoprostone; D011070:Poly I-C
keywords: PGE2; RNA electroporation; chemokine; chemokine receptor; cytokine cocktail; dendritic cells; migration; ‘improved’