@article{oai:hirosaki.repo.nii.ac.jp:00003621,
 author = {Seya, Tsukasa and Matsumoto, Misako and Ebihara, Takashi and Akazawa, Takashi},
 issue = {Supplement},
 journal = {弘前医学},
 month = {Nov},
 note = {application/pdf, Double-stranded （ds）RNA-recognition receptors reside in the cytoplasm and membranes of cells. These
receptors are implicated in the differential screening of microbes by the host. Myeloid dendritic cells （mDCs）
recognize and respond to polyI:C, an analog of dsRNA, by endosomal TLR3 and cytoplasmic MDA5. NK cells are
induced in vivo by the administration of polyI:C to mice and in vitro are reciprocally activated by mDCs, although the
molecular mechanisms as yet undetermined. Here, we show that the TLR adapter TICAM-1 （TRIF） participates in
mDC-derived antitumor NK activation. In a syngeneic mouse tumor implant model, intraperitoneal administration of
polyI:C led to the retardation of tumor growth, which eff ect relied largely on NK activation. This NK-dependent tumor
regression did not occur in TICAM-1-/- or IFNAR-/- mice, while a normal NK antitumor response was induced in PKR-/-,
MyD88-/-, IFN-β-/- and wild-type mice. IFNAR was a prerequisite for the induction of IFN-α/β and TLR3. The lack
of TICAM-1 did not aff ect IFN production but resulted in unresponsiveness to IL-12 production, mDC maturation and
polyI:C-mediated antitumor activity. This NK activation required NK-mDC contact in in vitro transwell analysis. NKantitumor
activity was successfully introduced into tumor-implanted mice by transferring mDCs expressing TICAM-1.
Implanted tumor growth in IFNAR-/- mice was retarded by adoptively transferring polyI:C-treated TICACM-1-positive
mDCs but not TICAM-1-/- mDCs. Thus, TICAM-1 rather than MDA5 in mDCs critically facilitated mDC-NK contact
and activation of antitumor NK, resulting in the regression of low MHC-expressing tumors, 弘前医学. 59(Suppl.), 2007, p.S43-S51},
 pages = {S43--S51},
 title = {NK-activating dendritic cells are elicited by stimulation with Toll-like receptor 3},
 volume = {59},
 year = {2007}
}