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Tumor immunotherapy using bone marrow-derived dendritic cells overexpressing Toll-like receptor adaptors

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タイトル: Tumor immunotherapy using bone marrow-derived dendritic cells overexpressing Toll-like receptor adaptors
著者: Akazawa, Takashi 著作を一覧する
Shingai, Masashi 著作を一覧する
Sasai, Miwa 著作を一覧する
Ebihara, Takashi 著作を一覧する
Inoue, Norimitsu 著作を一覧する
Matsumoto, Misako 著作を一覧する
Seya, Tsukasa 著作を一覧する
キーワード: Densritic cell therapy
Adoptive transfer
発行日: 2007年 7月24日
出版者: Elsevier B.V.
誌名: FEBS Letters
巻: 581
号: 18
開始ページ: 3334
終了ページ: 3340
出版社 DOI: 10.1016/j.febslet.2007.06.019
抄録: Myeloid dendritic cells (mDCs) play an important role in the initiation of immune responses to cancer and infectious diseases. Toll-like receptors (TLRs) expressed on mDCs recognize microbial products to elicit signals for mDC maturation, including cytokine production, antigen-presentation and induction of effector cells. TLR agonists work as adjuvants to modulate the function of mDCs. In TLR signaling, MyD88 and TRIF/TICAM-1 are major TLR adaptor molecules, which when overexpressed are able to transduce downstream signals without TLR stimuli. We successfully introduced the adaptors into mouse bone marrowderived mDCs using lentiviral vectors. Introduction of MyD88 into mDCs in vitro led to the production of IL-6 and IL-12p40 while introduction of TICAM-1 stimulated interferon (IFN)-alpha production. Expression of TICAM-1, but not MyD88, in mDCs slightly induced the co-stimulatory molecule CD86, while significant upregulation of CD86 was observed in response to other TLR stimuli. Both MyD88 and TICAM-1 augmented allogeneic mixed lymphocyte reaction (MLR). Ex vivo mouse spleen cells pre-exposed to tumor antigen exhibited antitumor cytotoxicity when incubated with MyD88- or TICAM-1-expressing mDCs. Using mDC adoptive transfer and a syngeneic mouse tumor implant model, we established an antitumor immunotherapy whereby tumor growth is retarded by adaptor-manipulated mDCs.
Relation (URI):
資料タイプ: article (author version)
出現コレクション:雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

提供者: 瀬谷 司


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