Clearance of Dead Tumor Cells and Tumor Immunity

肿瘤细胞被认为是“改变的自我”，因为它们积累了基因突变，并获得了使它们能够逃避免疫监视的特征。肿瘤定向细胞毒性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，抗原呈递细胞（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如何获得和交叉表达这些抗原知之甚少。我们发现，CD169^+巨噬细胞吞噬通过淋巴流转运的死亡肿瘤细胞，并随后吞噬CD8 T细胞。照射肿瘤细胞皮下免疫保护小鼠免受同系肿瘤。然而，在CD169^+巨噬细胞耗竭的小鼠中，肿瘤抗原特异性CD8 T细胞活化和随后的抗肿瘤免疫严重受损。迁移性树突状细胞（DC）和淋巴结驻留的常规DC都不是肿瘤抗原交叉表达所必需的。因此，我们已经鉴定出淋巴结CD169^+巨噬细胞是一种新的APC亚群，其主导肿瘤抗原特异性CD8 T细胞的早期活化。

Tumor cells are considered' altered self' because they accumulate genetic mutations and acquire features that enable them to evade immune surveillance. The generation of tumor-directed cytotoxic T lymphocytes is considered crucial for the induction of anti-tumor 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 crossprime CD8 T cells. Subcutaneous immunization with irradiated tumor cells protects mice from syngenic tumor. However, tumor antigen-specific CD8 T cell activation and subsequent anti-tumor 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 lymph node CD169^+macrophages as a novel APC subset dominating early activation of tumor antigen-specific CD8 T cells.