Granulocyte Colony-stimulating Factor Suppresses Autologous Tumor Killing Activity of the Peripheral Blood Lymphocytes in the Patients with Ovarian Carcinoma

• Published in: American journal of reproductive immunology (1989) Vol. 52; no. 1; pp. 81 - 87
• Main Authors: Ohta, Yoshiaki, Hayakawa, Satoshi, Karasaki-Suzuki, Miki, Sugita, Kenji, Komine, Shihoko, Chishima, Fumihisa, Hatta, Yoshihiro, Horie, Takashi, Seo, Naohiro, Sheikh, Aleemuzzaman, Nemoto, Norimichi, Yamamoto, Tatsuo
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing 01-07-2004
• Subjects: ATK; Cytotoxicity, Immunologic - drug effects; Female; G-CSF; Granulocyte Colony-Stimulating Factor - metabolism; Granulocyte Colony-Stimulating Factor - pharmacology; Humans; IFN-γ; Interferon-gamma - biosynthesis; Interferon-gamma - immunology; Interleukin-12 - pharmacology; Interleukin-2 - pharmacology; Lymphocytes - drug effects; Lymphocytes - immunology; ovarian carcinoma; Ovarian Neoplasms - immunology; Ovarian Neoplasms - pathology; Receptors, Granulocyte Colony-Stimulating Factor - genetics; RNA, Messenger - genetics; RNA, Messenger - metabolism; Tumor Cells, Cultured
• ISSN: 1046-7408; 1600-0897
• DOI: 10.1111/j.1600-0897.2004.00191.x

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)‐γ 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‐γ 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‐γ production. The frequency of IFN‐γ 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‐γ 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.