演題詳細

一般口演 / Oral Session

一般口演 105 (Oral Session 105) :免疫制御

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日程
2013年10月13日(日)
時間
15:00 - 16:00
会場
第13会場 / Room No.13 (札幌市教育文化会館 3F 研修室301)
座長・司会
渋谷 彰 (Akira Shibuya):1
1:筑波大学医学医療系 免疫学
 
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TLR7 ligand overcomes therapeutic resistance to GM-CSF-gene transduced tumor vaccination

演題番号 : OS-3-172

成澤 慈 (Megumi Narusawa):1、井上 博之 (Hiroyuki Inoue):1,2、坂本 千香 (Chika Sakamoto):1、井上 朋子 (Tomoko Inoue):1、宮本 将平 (Shohei Miyamoto):1、井上 誠 (Makoto Inoue):3、高山 浩一 (Koichi Takayama):2、長谷川 護 (Mamoru Hasegawa):2、中西 洋一 (Yoichi Nakanishi):2、谷 憲三朗 (Kenzaburo Tani):1

1:Molecular Clinical Genetics, Medical Institute of Bioregulation, Kyushu University, Japan、2:Research Institute for Diseases of the Chest, Fukuoka, Japan、3:DNAVEC Corporation, Tsukuba, Japan

 

Although GM-CSF (granulocyte macrophage-colony stimulating factor) gene-transduced tumor cell vaccines (GVAX) have been shown to provoke substantial antitumor immunity, its efficacies were limited. These vaccines induce the robust accumulation and activation of dendritic cells (DCs) in peripheral tissues. However, little is known about the key factors involved in GM-CSF-sensitized DCs (GM-DCs) in tumor-draining lymph nodes (TDLNs). We initially confirmed that mice subcutaneously injected with Lewis lung carcinoma (LLC) cells transduced with Sendai virus encoding GM-CSF (LLC/SeV/GM) significantly rejected the tumor growth. Using cDNA microarrays, we obtained a large number of gene expression data from mature GM-DCs and control DCs in TDLNs, and found the expression levels of type I IFNs-related genes including TLR7 and IRF7 which highly expressed in plasmacytoid DCs (pDCs) were robustly upregulated in GM-DCs. These results indicated that involvement of pDCs in GM-CSF-induced antitumor immunity. Indeed, pDCs-depleted mice inoculated with LLC/SeV/GM cells abrogated the GM-CSF-triggered antitumor effects. Furthermore, combination use of TLR7 ligand imiquimod and irradiated LLC/SeV/GM cells induced a significant therapeutic antitumor effect whereas control groups had not. Moreover, similar results were obtained when we used CT26 mouse colon cancer cell line. Taken together, our data demonstrated that pDCs play an essential role in GM-CSF-induced antitumor immunity, suggesting that activation of pDCs may be effective to break down the immune tolerance by GVAX therapy.

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