期刊
JOURNAL OF IMMUNOLOGY
卷 176, 期 1, 页码 157-164出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.176.1.157
关键词
-
类别
资金
- NATIONAL CANCER INSTITUTE [R01CA127565, T32CA009120, R01CA084008, R25CA098010] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P30DK041301] Funding Source: NIH RePORTER
- NCI NIH HHS [T32 CA09120-28, R01 CA127565, CA-84008-01, R25 CA 098010] Funding Source: Medline
- NIDDK NIH HHS [2P30DK041301] Funding Source: Medline
- NIGMS NIH HHS [GM07104] Funding Source: Medline
- PHS HHS [5-T32 A1007126-27] Funding Source: Medline
Immunotherapy represents an appealing option to specifically target CNS tumors using the immune system. In this report, we tested whether adjunctive treatment with the TLR-7 agonist imiquimod could augment antitumor immune responsiveness in CNS tumor-bearing mice treated with human gp100 + tyrosine-related protein-2 melanoma-associated Ag peptide-pulsed dendritic cell (DC) vaccination. Treatment of mice with 5% imiquimod resulted in synergistic reduction in CNS tumor growth compared with melanoma-associated Ag-pulsed DC vaccination alone. Continuous imiquimod administration in CNS tumor-bearing mice, however, was associated with the appearance of robust innate immune cell infiltration and hemorrhage into the brain and the tumor. To understand the immunological mechanisms by which imiquimod augmented antitumor immunity, we tested whether imiquilmod treatment enhanced DC function or the priming of tumor-specific CD8(+) T cells in vivo. With bioluminescent, in vivo imaging, we determined that imiquimod dramatically enhanced both the persistence and trafficking of DCs into the draining lymph nodes after vaccination. We additionally demonstrated that imiquimod administration significantly increased the accumulation of tumor-specific CD8(+) T cells in the spleen and draining lymph nodes after DC vaccination. The results suggest that imiquirnod positively influences DC trafficking and the priming of tumor-specific CD8(+) T cells. However, inflammatory responses induced in the brain by TLR signaling must also take into account the local microenvironment in the context of antitumor immunity to induce clinical benefit. Nevertheless, immunotherapeutic targeting of malignant CNS tumors may be enhanced by the administration of the innate immune response modifier imiquimod.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据