The TLR7 agonist imiquimod enhances the anti-melanoma effects of a recombinant Listeria monocytogenes vaccine
The TLR7 agonist imiquimod enhances the anti-melanoma effects of a recombinant Listeria monocytogenes vaccine
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DOI：
10.4049/jimmunol.175.3.1983
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发表时间：
2005-08-01
影响因子：
4.4
通讯作者：
Miller, JF
中科院分区：
文献类型：
--
作者：
Craft, N;Bruhn, KW;Miller, JF
通过TLR激活先天性免疫细胞触发增强细胞介导的免疫的免疫调节事件，提高了这些受体的配体可能与T细胞活化疫苗一起充当佐剂的可能性。在这份报告中，局部咪喹莫特，一种合成的TLR7激动剂，显着增强了保护性的抗肿瘤作用的活的，重组的阿伐他汀疫苗对小鼠黑色素瘤。这种肿瘤保护作用不依赖于直接应用于肿瘤，并且与肿瘤相关和脾树突状细胞的增加有关。此外，咪喹莫特治疗与先前疫苗接种的组合导致局部白癜风的发展。这些发现表明，用TLR配体激活先天免疫系统刺激树突细胞活性，导致绕过外周耐受和增强的抗肿瘤活性。这些研究的结果对未来设计抗肿瘤免疫疫苗和治疗转移性黑色素瘤具有广泛的意义。
Activation of innate immune cells through TLR triggers immunomodulating events that enhance cell-mediated immunity, raising the possibility that ligands to these receptors might act as adjuvants in conjunction with T cell activating vaccines. In this report, topical imiquimod, a synthetic TLR7 agonist, significantly enhanced the protective antitumor effects of a live, recombinant listeria vaccine against murine melanoma. This tumor protective effect was not dependent on direct application to the tumor and was associated with an increase in tumor-associated and splenic dendritic cells. Additionally, the combination of imiquimod treatment with prior vaccination led to development of localized vitiligo. These findings indicate that activation of the innate immune system with TLR ligands stimulates dendritic cell activity resulting in a bypass of peripheral tolerance and enhanced antitumor activity. The results of these studies have broad implications for future designs of immunotherapeutic vaccines against tumors and the treatment of metastatic melanoma.