In vivo anti- and pro-tumour activities of the TLR2 ligand FSL-1
In vivo anti- and pro-tumour activities of the TLR2 ligand FSL-1
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DOI：
10.1016/j.imbio.2011.02.006
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发表时间：
2011-08-01
期刊：
影响因子：
2.8
通讯作者：
Shibata, Ken-ichiro
中科院分区：
文献类型：
--
作者：
Kiura, Kazuto;Hasebe, Akira;Shibata, Ken-ichiro
TLR配体作为Th1诱导剂作为潜在的抗肿瘤药物已被研究。然而，很少有人尝试研究TLR配体作为Th2诱导剂的抗肿瘤活性。因此，本研究旨在确定TLR2配体FSL-1作为Th2诱诱剂是否影响来自C57BL/6 （TLR2(+/+)）小鼠的QRsP肿瘤（纤维肉瘤）的生长。同时免疫FSL-1和肿瘤相关抗原的TLR2（+/+）小鼠的肿瘤体积明显小于对照小鼠。同时免疫FSL-1和肿瘤相关抗原可提高TLR2（+/+）小鼠的存活率。然而，令人惊讶的是，单独接种FSL-1可显著促进肿瘤的生长。在TLR2（-/-）小鼠中未观察到FSL-1的抗肿瘤和促肿瘤活性。FSL-1和肿瘤相关抗原的免疫诱导肿瘤相关抗原特异性细胞溶解T细胞，通过产生肿瘤特异性抗体产生的抗体依赖细胞介导的自然杀伤细胞的细胞毒性，通过补体激活和引流淋巴结中调节性T细胞数量的减少诱导肿瘤溶解。单独用FSL-1免疫可增加引流淋巴结中调节性T细胞的数量，而在小鼠体内给药抗cd25抗体可消除FSL-1的促肿瘤活性，提示调节性T细胞参与促肿瘤活性。本研究表明，FSL-1分别在免疫肿瘤相关抗原和不免疫肿瘤相关抗原时表现出tlr2介导的抗肿瘤和促肿瘤活性。(C) 2011爱思唯尔有限公司版权所有。
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. (C) 2011 Elsevier GmbH. All rights reserved.