title: Granulocyte colony-stimulating factor suppresses autologous tumor killing activity of the peripheral blood lymphocytes in the patients with ovarian carcinoma.
abstract: OBJECTIVE
  Granulocyte colony-stimulating factor (G-CSF) is often administered to patients with chemotherapy-induced leukocytopenia. However, adequate attention has not been paid to its effects on cancer immunology. Reported by us and others, G-CSF often induces immunosuppression and down-regulation of response T helper (Th)2 directed immune reaction both in vivo and in vitro. In this study, we analyzed the effects of G-CSF on interferon (IFN)-gamma production and autologous tumor killing (ATK) activities of peripheral blood mononuclear cells (PBMCs).
  
  
  METHODS
  In order to evaluate the cytokine-induced activation of peripheral T and natural killer (NK) cells, we analyzed IFN-gamma production by interleukin (IL)-2- and IL-12-stimulated PBMCs, using the ELISPOT assay. Specific killing of autologous tumor cells was evaluated by lactate dehydrogenase (LDH) release assay.
  
  
  RESULTS
  The PBMC collected from both cancer-bearing patients and healthy subjects showed IL-2- and/or IL-12-induced IFN-gamma production. The frequency of IFN-gamma producing cells was significantly higher in the normal subjects compared with the patients with advanced ovarian carcinoma. The ATK activity was also enhanced in IL-2- and/or IL-12-stimulated PBMCs of patients with ovarian carcinoma. G-CSF almost completely abolished IFN-gamma production and ATK activity of PBMC stimulated with IL-2 and/or IL-12.
  
  
  CONCLUSIONS
  The G-CSF appears to be a suppressor of antitumor immunity. Routine administration of G-CSF to cancer patients may not be recommended, except for febrile neutropenia.
authors.affiliation: Department of Obstetrics and Gynecology, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ohta
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hayakawa
authors.forename: Miki
authors.initials: M
authors.lastname: Karasaki-Suzuki
authors.forename: Kenji
authors.initials: K
authors.lastname: Sugita
authors.forename: Shihoko
authors.initials: S
authors.lastname: Komine
authors.forename: Fumihisa
authors.initials: F
authors.lastname: Chishima
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hatta
authors.forename: Takashi
authors.initials: T
authors.lastname: Horie
authors.forename: Naohiro
authors.initials: N
authors.lastname: Seo
authors.forename: Aleemuzzaman
authors.initials: A
authors.lastname: Sheikh
authors.forename: Norimichi
authors.initials: N
authors.lastname: Nemoto
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Yamamoto
mesh_terms: D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D018664:Interleukin-12 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D007376:Interleukin-2; D012333:RNA, Messenger; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016179:Granulocyte Colony-Stimulating Factor; D018664:Interleukin-12; D007371:Interferon-gamma