Granulocyte colony-stimulating factor suppresses autologous tumor killing activity of the peripheral blood lymphocytes in the patients with ovarian carcinoma.
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.
Ohta
Yoshiaki
Y
Department of Obstetrics and Gynecology, Nihon University School of Medicine, Tokyo, Japan.
Hayakawa
Satoshi
S
Karasaki-Suzuki
Miki
M
Sugita
Kenji
K
Komine
Shihoko
S
Chishima
Fumihisa
F
Hatta
Yoshihiro
Y
Horie
Takashi
T
Seo
Naohiro
N
Sheikh
Aleemuzzaman
A
Nemoto
Norimichi
N
Yamamoto
Tatsuo
T
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
D007376:Interleukin-2; D012333:RNA, Messenger; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016179:Granulocyte Colony-Stimulating Factor; D018664:Interleukin-12; D007371:Interferon-gamma