title: Interferon alpha induces generation of semi-mature dendritic cells with high pro-inflammatory and cytotoxic potential.
abstract: Dendritic cell-based vaccines are considered as a new and promising immunotherapeutic approach for cancer treatment. However, the choice of optimal protocol of dendritic cell generation in vitro represents the major challenge. Here, we compared phenotype and functional characteristics of human monocyte-derived dendritic cells (DCs) generated in the presence of IL-4/GM-CSF (IL4-DCs) and IFNα/GM-CSF (IFN-DCs). We showed that IFN-DCs displayed semi-mature phenotype and expressed higher level of CD123, TNF-related apoptosis-inducing ligand (TRAIL) and B7-H1 molecules in comparison with IL4-DCs. LPS-stimulated IFN-DCs were characterized by greater production of Th1/pro-inflammatory (IFN-γ, IL-2, IL-1β, TNF-α, IL-17), Тh2/anti-inflammatory cytokines (IL-10, IL-5), hematopoietic growth factors (G-CSF) and chemokines (MCP-1). These data indicated more pronounced ability of IFN-DCs to induce cellular immune response as well as humoral immune response compared to IL4-DCs. LPS-stimulated IFN-DCs possessed higher direct cytotoxic activity against TRAIL-sensitive tumor cell line Jurkat and similar cytotoxicity against TRAIL-resistant tumor HEp-2 cells. Besides, IFN-DCs and IL4-DCs equally induced apoptosis of activated CD4(+) and CD8(+) T cells. These results suggest that IFN-DCs can be used as potent cell-based curative therapies for individuals with cancer.
authors.affiliation: Institute of Clinical Immunology SB RAMS, 14 Yadrintsevskaya Str., 630099 Novosibirsk, Russia(1).
authors.forename: Olga Yu
authors.initials: OY
authors.lastname: Leplina
authors.affiliation: Institute of Clinical Immunology SB RAMS, 14 Yadrintsevskaya Str., 630099 Novosibirsk, Russia(1). Electronic address: tyrinova@gmail.com.
authors.forename: Tamara V
authors.initials: TV
authors.lastname: Tyrinova
authors.affiliation: Institute of Clinical Immunology SB RAMS, 14 Yadrintsevskaya Str., 630099 Novosibirsk, Russia(1).
authors.forename: Marina A
authors.initials: MA
authors.lastname: Tikhonova
authors.affiliation: Institute of Clinical Immunology SB RAMS, 14 Yadrintsevskaya Str., 630099 Novosibirsk, Russia(1).
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Ostanin
authors.affiliation: Institute of Clinical Immunology SB RAMS, 14 Yadrintsevskaya Str., 630099 Novosibirsk, Russia(1).
authors.forename: Elena R
authors.initials: ER
authors.lastname: Chernykh
mesh_terms: D017209:Apoptosis; D060890:B7-H1 Antigen / Q000235:genetics / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D018925:Chemokines / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism*; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation; D010641:Phenotype; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; D018925:Chemokines; D016207:Cytokines; C508598:IL4 protein, human; D016898:Interferon-alpha; D008070:Lipopolysaccharides; C439524:TNF protein, human; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: B7-H1; Cytotoxic activity; Dendritic cells; IFN alpha; TRAIL