期刊
JOURNAL OF IMMUNOLOGY
卷 175, 期 3, 页码 1983-1990出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.175.3.1983
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资金
- NCI NIH HHS [R01 CA84008-01, R01 CA127565] Funding Source: Medline
- NIGMS NIH HHS [GM07104] Funding Source: Medline
- PHS HHS [5 T32 A1007126-27] Funding Source: Medline
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.
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