Granulocyte colony-stimulating factor suppresses autologous tumor killing activity of the peripheral blood lymphocytes in the patients with ovarian carcinoma

PROBLEM: 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 OF STUDY: 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.