| Co-Investigator(Kenkyū-buntansha) |
TAKENAGA Keizo Division of Chemotherapy, Chiba Cancer Center, Chief Scientist, 化学療法部, 研究員 (80260256)
磯野 可一 千葉大学, 医学部, 教授 (70009489)
OCHIAI Takenori Department of Surgery(II), Chiba University, School of Medicine, Professor, 医学部, 助教授 (80114255)
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| Research Abstract |
(1) We examined whether cytokine-mediated immune responses are actively involved in antitumor effects on gastrointestinal tumors. To augment the activity of Th1-type T cells which play crucial roles in antitumor immunity, we introduced several cytokine genes (IL-12, IL-15 and IL-18) in murine colon carcinoma cells. IL-12 and IL-18 mediate differentiation and maturation steps of Th1-type T cells, and IL-15, a novel cytokine, are secreted from Th1-type T cells. In vivo tumorigenicity was tested by inculating these cytokine producer cells into syngeneic or immunocompromised mice. All the cytokine producer cells showed antitumor effect in various circumstances, in particular, we showed that mature T cells were indispensable in every case. In the case of IL-12 producing cells, granulocytes and/or macrophages were also involved in the antitumor activity and enhanced expression of adhesion molecules in the endothelium of peritumoral regions was observed. In contrast, IL-18 producing tumors which shares the same properties-ability to produce interferon gammma-as IL-12 producing tumors, did not require granulocytes or macrophages for their antitumor activities. Natural killer cells are primary effector cells in IL-15 producing tumors. (2) IL-10, a Th2-type cytokine, is regarded to inhibit cellular immunity.
Expression of IL-10 gene in murine colon carcinoma cells actively suppressed systemic immune responses in the inoculated mice and this suppression was also observed in mature T cells-deficient conditions. Th1-mediated immune responses, which is brough by forced expression of Th1-type cytokine genes, could not fully restore this immune tolerance.
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