title: In vivo anti- and pro-tumour activities of the TLR2 ligand FSL-1.
abstract: TLR ligands as Th1 inducers have been investigated as potential anti-tumour agents. However, few attempts have been made to investigate the anti-tumour activity of TLR ligands as Th2 inducers. This study, therefore, was carried out to determine whether the TLR2 ligand FSL-1 as a Th2 inducers affects the growth of a QRsP tumour, a fibrosarcoma derived from the C57BL/6 (TLR2(+/+)) mouse in vivo. Tumour volumes in TLR2(+/+) mice immunized with both FSL-1 and tumour-associated antigens were significantly smaller than those in control mice. Immunization with both FSL-1 and tumour-associated antigens increased the survival rate of TLR2(+/+) mice. However, surprisingly, immunization with FSL-1 alone significantly enhanced the growth of tumour. Both anti- and pro-tumour activities of FSL-1 were not observed in TLR2(-/-) mice. Immunization of both FSL-1 and tumour-associated antigens induced tumour-associated antigen-specific cytolytic T cells, antibody-dependent cell-mediated cytotoxicity of natural killer cells by production of the tumour-specific antibodies, tumour lysis by complement activation and reduction of the number of regulatory T cells in the draining lymph node. Immunization with FSL-1 alone increased the number of regulatory T cells in the draining lymph node, and in vivo administration of anti-CD25 antibody into mice abrogated the pro-tumour activity of FSL-1, suggesting that regulatory T cells are involved in the pro-tumour activity. This study demonstrated that FSL-1 exhibited TLR2-mediated anti- and pro-tumour activities when immunized with and without tumour-associated antigens, respectively.
authors.affiliation: Division of Oral Molecular Microbiology, Department of Oral Pathobiological Science, Hokkaido University Graduate School of Dental Medicine, Kita 13, Nishi 7, Kita-ku, Sapporo 060-8586, Japan.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Kiura
authors.forename: Akira
authors.initials: A
authors.lastname: Hasebe
authors.forename: Ayumi
authors.initials: A
authors.lastname: Saeki
authors.forename: Taku
authors.initials: T
authors.lastname: Segawa
authors.forename: Futoshi
authors.initials: F
authors.lastname: Okada
authors.forename: Haque Mohammad
authors.initials: HM
authors.lastname: Shamsul
authors.forename: Makoto
authors.initials: M
authors.lastname: Ohtani
authors.forename: Takeshi
authors.initials: T
authors.lastname: Into
authors.forename: Nobuo
authors.initials: N
authors.lastname: Inoue
authors.forename: Minoru
authors.initials: M
authors.lastname: Wakita
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Shibata
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000494:pharmacology; D018791:CD4 Lymphocyte Count; D045744:Cell Line, Tumor; D003167:Complement Activation / Q000187:drug effects / Q000276:immunology; D005354:Fibrosarcoma / Q000276:immunology* / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000517:prevention & control; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007114:Immunization; D053645:Interleukin-2 Receptor alpha Subunit / Q000037:antagonists & inhibitors / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008198:Lymph Nodes; D008222:Lymphokines / Q000276:immunology / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009368:Neoplasm Transplantation; D015996:Survival Rate; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051195:Toll-Like Receptor 2 / Q000276:immunology* / Q000378:metabolism
chemical_list: D000906:Antibodies; D000951:Antigens, Neoplasm; D053645:Interleukin-2 Receptor alpha Subunit; D008222:Lymphokines; D051195:Toll-Like Receptor 2; C085978:fibroblast stimulating factor-1