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题名: Combination of FasL and GM-CSF Confers Synergistic Antitumor Immunity in an In Vivo Model of the Murine Lewis Lung Carcinoma
作者: Ming-Yi Ho;Guang-Huan Sun;Shr-Jeng Jim Leu;Shuk-Man Ka;Shye-Jye Tang;Kuang-Hui Sun
贡献者: NTOU:Institute of Bioscience and Biotechnology
关键词: lung cancer;Fas ligand (FasL);granulocyte–macrophage-colony stimulating factor (GM-CSF);Th1 immune response
日期: 2008-07-01
上传时间: 2011-10-21T02:22:23Z
出版者: International Journal of Cancer
摘要: Abstract:Gene transfer of Fas ligand (FasL) to tumor cells has been demonstrated to inhibit tumor growth in vivo, and neutrophils are primarily responsible for this immunoprotection. The granulocyte–macrophage colony stimulating factor (GM-CSF) secreted by tumor vaccine can recruit dendritic cells (DCs) for efficient antigen presentation to T cells that generate the tumor-specific response. To investigate whether the combination of FasL and GM-CSF can efficiently suppress tumor growth, we have established Lewis lung carcinoma (LLC-1) cells that are transduced with GM-CSF (LLC/GM-CSF), FasL (LLC/FasL) or both genes (LLC/FasL/GM-CSF) to test their tumorigenic potential in vivo. Mice inoculated with LLC/GM-CSF display high survival rates along with reduction of tumor growth. In contrast, none of the mice injected with LLC/FasL or LLC/FasL/GM-CSF develop tumors. Specific memory immune response and delayed LLC-1 tumor growth are found in mice immunized with LLC-1/FasL or LLC-1/FasL/GM-CSF. Furthermore, therapeutic effects are observed only when LLC-1/FasL/GM-CSF tumor vaccine is employed to retard growth of preexisting LLC-1 tumors. Tumor growth is also completely suppressed in mice injected with a mixture of LLC-1 and LLC-1/FasL/GM-CSF. In addition, IL-12 production, cytotoxic T-cell activity and IgG against LLC-1 are manifested in mice injected with LLC/FasL/GM-CSF. Our data show that FasL-induced pathway triggers expression of proinflammatory cytokines, including IL-1β, IL-6, MIP-2 and MCP-1, while GM-CSF-dependent pathway promotes functional maturation and activation of DCs. Taken together, the results indicate that dual gene-based delivery with FasL and GM-CSF may serve as a more effective tumor vaccine to suppress lung cancer cell growth in vivo.
關聯: 123(1), pp.123–133
显示于类别:[生命科學暨生物科技學系] 期刊論文


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