TY - JOUR
T1 - In vivo anti- and pro-tumour activities of the TLR2 ligand FSL-1
AU - Kiura, Kazuto
AU - Hasebe, Akira
AU - Saeki, Ayumi
AU - Segawa, Taku
AU - Okada, Futoshi
AU - Shamsul, Haque Mohammad
AU - Ohtani, Makoto
AU - Into, Takeshi
AU - Inoue, Nobuo
AU - Wakita, Minoru
AU - Shibata, Ken ichiro
N1 - Funding Information:
This work was supported by Grants-in-Aid for Scientific Research B19390477 , B22390352 and C19592166 provided by the Japan Society for the Promotion of Science.
PY - 2011/8
Y1 - 2011/8
N2 - 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.
AB - 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.
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U2 - 10.1016/j.imbio.2011.02.006
DO - 10.1016/j.imbio.2011.02.006
M3 - Article
C2 - 21496943
AN - SCOPUS:79959499736
VL - 216
SP - 891
EP - 900
JO - Zeitschrift für Immunitätsforschung und experimentelle Therapie
JF - Zeitschrift für Immunitätsforschung und experimentelle Therapie
SN - 0171-2985
IS - 8
ER -