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Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Life Science / Faculty of Advanced Life Science >
Peer-reviewed Journal Articles, etc >
Tumor immunotherapy using bone marrow-derived dendritic cells overexpressing Toll-like receptor adaptors
| 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 | | TRIF/TICAM-1 | | MyD88 | | Adoptive transfer | | Lentivirus |
| 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. |
| Relation: | http://www.sciencedirect.com/science/journal/00145793 |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/30158 |
| 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)
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Submitter: 瀬谷 司
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