title: The Hedgehog inhibitor suppresses the function of monocyte-derived dendritic cells from patients with advanced cancer under hypoxia.
abstract: Immunotherapy using monocyte derived dendritic cells (Mo-DCs) from cancer patients has been developed; however, the Mo-DCs regularly studied have been derived from non-cancer bearing donors or mice, and evaluated in normoxic conditions. In the present study, we investigated the effects of Hedgehog (Hh) inhibitors which are being developed as molecular target drugs for cancer on the functions of Mo-DCs derived from patients with advanced cancer when cultured in a tumor-like hypoxic environment. Mo-DC induction, migration, chemotaxis, phagocytosis, maturation, IL-12 p40 or p70 secretion and the allogeneic lymphocyte stimulation activity of Mo-DCs from patients with advanced cancer were all significantly inhibited by the Hh inhibitor, cyclopamine under hypoxic conditions. Our results suggest that Hh signaling plays an important role in the maintenance and function of Mo-DCs derived from patients with advanced cancer when cultured under hypoxic conditions.
authors.affiliation: Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. ohnishi@surg1.med.kyushu-u.ac.jp
authors.forename: Hideya
authors.initials: H
authors.lastname: Onishi
authors.forename: Takashi
authors.initials: T
authors.lastname: Morisaki
authors.forename: Akifumi
authors.initials: A
authors.lastname: Kiyota
authors.forename: Norihiro
authors.initials: N
authors.lastname: Koya
authors.forename: Hiroto
authors.initials: H
authors.lastname: Tanaka
authors.forename: Masayo
authors.initials: M
authors.lastname: Umebayashi
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Katano
mesh_terms: D000328:Adult; D000368:Aged; D017951:Antigen Presentation; D015687:Cell Hypoxia; D002465:Cell Movement; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000166:cytology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism; D053762:Interleukin-12 Subunit p40 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014704:Veratrum Alkaloids / Q000494:pharmacology
chemical_list: D053823:Hedgehog Proteins; D053762:Interleukin-12 Subunit p40; D014704:Veratrum Alkaloids; D018664:Interleukin-12; C000541:cyclopamine