title: Effect of soluble factors derived from oral cancer cells on the production of interferon-γ from peripheral blood mononuclear cells following stimulation with OK-432.
abstract: The streptococcal antitumor agent OK-432 is commonly used as an immunopotentiator for immunotherapy in various types of malignant tumors including oral cancer. It has been demonstrated that OK-432 elicits an antitumor effect by stimulating immunocompetent cells, thereby inducing multiple cytokines including interferon (IFN)-γ, interleukin (IL)-2 and IL-12. Serum concentrations of IFN-γ in patients with oral cancer were examined 24 h after administration of OK-432. Serum concentrations of IFN-γ in patients with advanced cancer were significantly lower than those in patients with early cancer. These results suggested that some soluble factors produced by cancer cells may inhibit IFN-γ production with OK-432. Thus, in the present study, an in vitro simulation model was established for the immune status of patients with oral cancer by adding conditioned medium (CM) derived from oral cancer cell lines into a culture of peripheral blood mononuclear cells (PBMCs) derived from a healthy volunteer. We investigated whether soluble factors derived from oral cancer cells affected IFN-γ production from PBMCs following stimulation with OK-432. PBMCs stimulated with OK-432 produced a large amount of IFN-γ; however, both IFN-γ production and cytotoxic activity from PBMCs induced by OK-432 were inhibited by the addition of CM in a dose-dependent manner. In order to examine these inhibitory effects against IFN-γ production, the contribution of inhibitory cytokines such as IL-4, IL-6, IL-10, transforming growth factor-β and vascular endothelial growth factor was investigated. However, neutralization of these inhibitory cytokines did not recover IFN-γ production inhibited by CM. These results indicated that unknown molecules may inhibit IFN-γ production from PBMCs following stimulation with OK-432.
authors.affiliation: Department of Oral Surgery, Subdivision of Molecular Oral Medicine, Division of Integrated Sciences of Translational Research, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8504, Japan. go.ohe@tokushima-u.ac.jp
authors.forename: Go
authors.initials: G
authors.lastname: Ohe
authors.forename: Akiko
authors.initials: A
authors.lastname: Sasai
authors.forename: Daisuke
authors.initials: D
authors.lastname: Uchida
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tamatani
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Nagai
authors.forename: Youji
authors.initials: Y
authors.lastname: Miyamoto
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001685:Biological Factors / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D009062:Mouth Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D010844:Picibanil / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001685:Biological Factors; D017077:Culture Media, Conditioned; D007378:Interleukins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D010844:Picibanil; D007371:Interferon-gamma