CCR4 is critically involved in effective antitumor immunity in mice bearing intradermal B16 melanoma
CCR4 is critically involved in effective antitumor immunity in mice bearing intradermal B16 melanoma
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DOI：
10.1016/j.canlet.2016.04.039
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发表时间：
2016-08-01
期刊：
影响因子：
9.7
通讯作者：
Nakayama, Takashi
中科院分区：
文献类型：
--
作者：
Matsuo, Kazuhiko;Itoh, Tatsuki;Nakayama, Takashi
CCR 4是由Treg细胞和Th 17细胞表达的主要趋化因子受体。虽然已知Treg细胞抑制抗肿瘤免疫，但最近已显示Th 17细胞增强抗肿瘤细胞毒性T淋巴细胞的诱导。在此，CCR 4缺陷小鼠在皮内接种B16-F10黑色素瘤细胞后显示出增强的肿瘤生长。在CCR 4缺陷小鼠中，虽然IFN-γ + CD 8+效应T细胞在肿瘤部位减少，但IFN-γ + CD 8 + T细胞和Th 17细胞在局部淋巴结中减少。在野生型小鼠中，发现被鉴定为CCR 4 + CD 44+记忆性Th 17的CD 4 +IL-17 A+细胞聚集在局部淋巴结中表达MDC/CCL 22（CCR 4的配体）的树突状细胞周围。化合物22，一种CCR 4拮抗剂，在用达卡巴嗪治疗的荷瘤小鼠中也增强肿瘤生长并减少局部淋巴结中的Th 17细胞。相反，CCR 6缺陷不影响肿瘤生长和局部淋巴结中Th 17细胞的数量。这些发现表明，CCR 4是关键参与区域淋巴结DC-Th 17细胞的相互作用，这是必要的Th 17细胞介导的诱导抗肿瘤CD 8+效应T细胞在小鼠B16黑色素瘤。(C)2016爱思唯尔爱尔兰有限公司版权所有。
CCR4 is a major chemokine receptor expressed by Treg cells and Th17 cells. While Treg cells are known to suppress antitumor immunity, Th17 cells have recently been shown to enhance the induction of antitumor cytotoxic T lymphocytes. Here, CCR4-deficient mice displayed enhanced tumor growth upon intradermal inoculation of B16-F10 melanoma cells. In CCR4-deficient mice, while IFN-gamma+CD8+ effector T cells were decreased in tumor sites, IFN-gamma+CD8+ T cells and Th17 cells were decreased in regional lymph nodes. In wild-type mice, CD4+IL-17A+ cells, which were identified as CCR4+CD44+ memory Th17, were found to be clustered around dendritic cells expressing MDC/CCL22, a ligand for CCR4, in regional lymph nodes. Compound 22, a CCR4 antagonist, also enhanced tumor growth and decreased Th17 cells in regional lymph nodes in tumor-bearing mice treated with Dacarbazine. In contrast, CCR6 deficiency did not affect the tumor growth and the numbers of Th17 cells in regional lymph nodes. These findings indicate that CCR4 is critically involved in regional lymph node DC-Th17 cell interactions that are necessary for Th17 cell-mediated induction of antitumor CD8+ effector T cells in mice bearing B16 melanoma. (C) 2016 Elsevier Ireland Ltd. All rights reserved.