title: Quick generation of fully mature dendritic cells from monocytes with OK432, low-dose prostanoid, and interferon-alpha as potent immune enhancers.
abstract: Dendritic cells (DCs) are one of the promising tools for enhancing antigen-specific immune responses in clinical settings. Many studies have been performed thus far to verify the efficacy of the DC vaccine in cancer patients; however, the responses have not always been satisfactory, partly because of DC incompetence. To obtain DCs potentially applicable for vaccination of cancer patients, our group sought to establish the strategy of DC generation mainly by modulating culture periods and maturation stimuli. Novel mature DCs that can be generated from monocytes within 3 days by using a combination of OK432 (Streptococcus pyogenes preparation), low-dose prostaglandin E2 (PGE2), and interferon-alpha (OPA-DCs) were developed. They strongly express CD83, CD86, and CCR7 and have potent ability to migrate to CCL21. In addition, they were able to activate natural killer and T helper 1 (TH1) cells and to induce peptide-antigen-specific cytotoxic T lymphocytes more significantly than monocyte-derived DCs stimulated with a conventional cytokine cocktail of tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, and PGE2 (monocyte-conditioned medium [MCM]-mimic DCs). The profound ability of OPA-DCs to stimulate these effectors is attributable to their higher expression of IL-12p70, IL-23, and IL-27 than MCM-mimic DCs, which was supported by the findings that the neutralization of IL-12p70 and IL-23 reduced the TH1 priming ability of OPA-DCs. Even when from advanced gastric or colonic cancer patients, OPA-DCs displayed abilities of migration and TH1 induction comparable to those from healthy subjects. Therefore, OPA-DCs may serve as a feasible vaccine with the potential to enhance TH1-dominant and cytolytic immune responses against cancers.
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Sakakibara
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kanto
authors.forename: Michiyo
authors.initials: M
authors.lastname: Inoue
authors.forename: Aki
authors.initials: A
authors.lastname: Kaimori
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yakushijin
authors.forename: Hideki
authors.initials: H
authors.lastname: Miyatake
authors.forename: Ichiyo
authors.initials: I
authors.lastname: Itose
authors.forename: Masanori
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Kuzushita
authors.forename: Naoki
authors.initials: N
authors.lastname: Hiramatsu
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Takehara
authors.forename: Akinori
authors.initials: A
authors.lastname: Kasahara
authors.forename: Norio
authors.initials: N
authors.lastname: Hayashi
mesh_terms: D000276:Adjuvants, Immunologic; D000368:Aged; D018929:Cell Culture Techniques / Q000379:methods*; D002465:Cell Movement / Q000276:immunology; D003110:Colonic Neoplasms / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology*; D015232:Dinoprostone / Q000276:immunology; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology* / Q000276:immunology; D010844:Picibanil / Q000276:immunology; D013274:Stomach Neoplasms / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D016898:Interferon-alpha; D010844:Picibanil; D015232:Dinoprostone