CD169-Positive Macrophages Dominate Antitumor Immunity by Crosspresenting Dead Cell-Associated Antigens
CD169-Positive Macrophages Dominate Antitumor Immunity by Crosspresenting Dead Cell-Associated Antigens
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DOI：
10.1016/j.immuni.2010.12.011
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发表时间：
2011-01-28
期刊：
影响因子：
32.4
通讯作者：
Tanaka, Masato
中科院分区：
文献类型：
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作者：
Asano, Kenichi;Nabeyama, Ami;Tanaka, Masato
肿瘤导向的细胞毒性T淋巴细胞的产生被认为是诱导抗肿瘤免疫的关键。为了激活这些CD8(+)T细胞，抗原提呈细胞(APC)必须首先获得肿瘤细胞相关抗原。肿瘤抗原的主要来源是死亡的肿瘤细胞，但对引流淋巴结中的APC如何获得和交叉传递这些抗原知之甚少。在这里，我们展示了CD169(+)巨噬细胞吞噬死亡的肿瘤细胞通过淋巴流运输，随后将肿瘤抗原交叉传递给CD8(+)T细胞。经照射的肿瘤细胞皮下免疫可保护小鼠免受同种肿瘤的侵袭。然而，在CD169(+)巨噬细胞耗尽的小鼠中，肿瘤抗原特异性CD8(+)T细胞的激活和随后的抗肿瘤免疫严重受损。无论是迁移性树突状细胞(DC)还是驻留在淋巴结中的常规DC，对于肿瘤抗原的交叉表达都不是必需的。因此，我们已经确定CD169(+)巨噬细胞是驻留在淋巴结中的APC，主导着肿瘤抗原特异性CD8(+)T细胞的早期激活。
The generation of tumor-directed cytotoxic T lymphocytes is considered crucial for the induction of antitumor immunity. To activate these CD8(+) T cells, antigen-presenting cells (APCs) must initially acquire tumor cell-associated antigens. The major source of tumor antigens is dead tumor cells, but little is known about how APCs in draining lymph nodes acquire and crosspresent these antigens. Here we show that CD169(+) macrophages phagocytose dead tumor cells transported via lymphatic flow and subsequently crosspresent tumor antigens to CD8(+) T cells. Subcutaneous immunization with irradiated tumor cells protects mice from syngenic tumor. However, tumor antigen-specific CD8(+) T cell activation and subsequent antitumor immunity are severely impaired in mice depleted with CD169(+) macrophages. Neither migratory dendritic cells (DCs) nor lymph node-resident conventional DCs are essential for the crosspresentation of tumor antigens. Thus, we have identified CD169(+) macrophages as lymph node-resident APCs dominating early activation of tumor antigen-specific CD8(+) T cells.