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

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Title: Tumor immunotherapy using bone marrow-derived dendritic cells overexpressing Toll-like receptor adaptors
Authors: Akazawa, Takashi Browse this author
Shingai, Masashi Browse this author
Sasai, Miwa Browse this author
Ebihara, Takashi Browse this author
Inoue, Norimitsu Browse this author
Matsumoto, Misako Browse this author →KAKEN DB
Seya, Tsukasa Browse this author →KAKEN DB
Keywords: Densritic cell therapy
Adoptive transfer
Issue Date: 24-Jul-2007
Publisher: Elsevier B.V.
Journal Title: FEBS Letters
Volume: 581
Issue: 18
Start Page: 3334
End Page: 3340
Publisher DOI: 10.1016/j.febslet.2007.06.019
PMID: 17601575
Abstract: 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.
Type: article (author version)
Appears in Collections:生命科学院・先端生命科学研究院 (Graduate School of Life Science / Faculty of Advanced Life Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 瀬谷 司

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