Clearance of Dead Tumor Cells and Tumor Immunity

死亡肿瘤细胞的清除和肿瘤免疫

• 批准号: 21790396
• 负责人: ASANO Kenichi
• 金额: $ 2.58万
• 依托单位: Tokyo University of Pharmacy and Life Science (2011)The Institute of Physical and Chemical Research (2009-2010)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21790396/
• 关键词: 腫瘍; リンパ節; CD169; マクロファージ; 死細胞; クロスプレゼンテーション; 免疫寛容; 貪食

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.

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CD8T细胞，抗原提呈细胞(APC)必须首先获得肿瘤细胞相关的抗原。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，随后跨膜CD8T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CD8T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，我们已确定淋巴结CD169^+巨噬细胞是一个新的APC亚群，主导肿瘤抗原特异性CD8T细胞的早期激活。

项目成果

CD169-Positive Macrophages Dominate Antitumor Immunity by Crosspresenting Dead Cell-Associated Antigens

• DOI: 10.1016/j.immuni.2010.12.011
• 发表时间: 2011-01-28
• 期刊: IMMUNITY
• 影响因子: 32.4
• 作者: Asano, Kenichi;Nabeyama, Ami;Tanaka, Masato
• 通讯作者: Tanaka, Masato

Role of CD169+Macrophages in the Crosspresentation of Cell-associated Antigens

CD169 巨噬细胞在细胞相关抗原交叉呈递中的作用

• 发表时间: 2010

Role of CD169+ macrophages in the crosspresentation of cell-associated antigens.

CD169 巨噬细胞在细胞相关抗原交叉呈递中的作用。

• 发表时间: 2010
• 作者: Asano;Kenichi
• 通讯作者: Kenichi

Macrophages dictate the direction of immune response against dead cell-associated antigens.

巨噬细胞决定针对死细胞相关抗原的免疫反应的方向。

• 发表时间: 2010
• 作者: Asano;Kenichi
• 通讯作者: Kenichi

Macrophages Dictate the Direction of Immune response against Dead Cell-associated Antigens

巨噬细胞决定针对死细胞相关抗原的免疫反应方向

• 发表时间: 2010