Effects of Interleukin-12 on the Induction of Cytotoxic T Lymphocytes from the Regional Lymph Node Lymphocytes of Patients with Lung Adenocarcinoma |
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Authors: | Takeshi Hanagiri Ichiro Yoshino Mitsuhiro Takenoyama Tomoko So Hiroshi Fujie Satoru Imabayashi Ryozo Eifuku Takashi Yoshimatsu Toshihiro Osaki Ryoichi Nakanishi Yuji Ichiyoshi Akira Nagashima Kikuo Nomoto Kosei Yasumoto |
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Affiliation: | Department of Surgery II, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807;Department of Chest Surgery, Kitakyushu Municipal Medical Center, 2-1-1 Bashaku, Kokurakita-ku, Kitakyushu 802;Department of Immunology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812 |
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Abstract: | Lung cancer-specific cytotoxic T lymphocytes (CTL) were induced by repeated stimulations of regional lymph node lymphocytes (RLNL) in lung cancer patients with either autologous or HLA-A-locus-matched tumor cells. To investigate the effect of interleukin-12 (IL-12), IL-12 was added during the stimulation of RLNL from HLA A24 / adenocarcinoma patients with either autologous tumor cells or HLA A24-positive adenocarcinoma cells (PC-9) in combination with, or instead of interleukin-2 (IL-2), and then the cytotoxic activity, cytokine production and populations of the lymphocyte subsets were examined. The addition of IL-12, or the substitution of IL-2 by IL-12 was found to enhance the cytotoxic activity and the cytokine production (IFN-γ, GM-CSF) of the CTL as compared with IL-2 alone. The cytotoxic activity and cytokine production were both partially inhibited by anti-MHC-class I monoclonal antibody. The CTL thus induced by IL-12 had a higher proportion of CD3+/CD56+ cells than the CTL induced with IL-2 alone. The positively selected CD8+/CD56– lymphocytes showed PC-9-specific cytotoxic activity, because the population did not show any cytotoxicity to K562 or A549 (HLA-A26/A30). However, the CD3+/CD56+ lymphocytes were cytotoxic to both PC-9 and K562. In conclusion, IL-12 is considered to be a useful cytokine for both the induction of lung-cancer specific CTL and the augmentation of non-MHC-restricted cytotoxicity against tumor cells, and may be applicable for adoptive immunotherapy using CTL. |
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Keywords: | Regional lymph node lymphocytes Interleukin-12 Cytotoxic T lymphocytes Lung cancer |
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