Okamoto, Masato Second Department of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry
Sato, Mitsunobu Second Department of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Toll-like receptor (TLR)
It is important to augment the anti-cancer host response in cancer treatment. Recent studies suggested that the signaling via Toll-like receptors (TLRs) which are newly identified receptor molecules recognizing many pathogens, are involved in the induction of anti-cancer immunity. Seya et al. demonstrated that maturation of dendritic cells(DCs) and cytokine induction by the cell wall skeleton of Mycobacterium bovis bacillus Calmette-Guérin (BCG-CWS) are induced via both TLR2 and TLR4. Akira et al. discovered a new molecule of TLR family, TLR9, recognizing unmethylated bacterial CpG-DNA, whose clinical use is expected for cancer therapy as a potent inducer of a helper T cell 1 (Th1)-typeT-cell response. TLR9-deficient mice did not show any responses to CpG-DNA, including Th 1 cytokine production and maturation of DCs. We have obtained two molecules, a lipoteichoic
acid-related molecule isolated from streptococcal agent OK-432, and a plant-derived 55-kDaprotein that can induce Th1 response and elicit a strong anti-cancer effect in vivo and in vitro. Our basic experiments demonstrate that TLR4 signaling is intimately involved in anti-cancer immunity induced by these immunopotentiators. Our clinical examination in oral cancer patients also suggests the requirement of both TLR4 and MD-2 in the OK-432-inducedanti-cancer host response. Establishment and clinical use of the methodology for human cancer therapy by utilizing TLR signaling is greatly expected.
The journal of medical investigation : JMI
jmi_50_1-2_9.pdf 251 KB