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肿瘤细胞的膜转移克服了浆细胞样树突状细胞吞噬能力的缺陷,使其能够获取和呈递肿瘤抗原。

Membrane transfer from tumor cells overcomes deficient phagocytic ability of plasmacytoid dendritic cells for the acquisition and presentation of tumor antigens.

机构信息

Laboratory of Immunology and Biotherapy, Department of Human Pathology, University of Messina, 98125 Messina, Italy;

出版信息

J Immunol. 2014 Jan 15;192(2):824-32. doi: 10.4049/jimmunol.1301039. Epub 2013 Dec 11.

Abstract

The potential contribution of plasmacytoid dendritic cells (pDCs) in the presentation of tumor cell Ags remains unclear, and some controversies exist with regard to the ability of pDCs to phagocytose cell-derived particulate Ags and cross-present them to MHC class I-restricted T lymphocytes. In this study, we show that human pDCs, although inefficient in the internalization of cell membrane fragments by phagocytosis, can efficiently acquire membrane patches and associated molecules from cancer cells of different histotypes. The transfer of membrane patches to pDCs occurred in a very short time and required cell-to-cell contact. Membrane transfer also included intact HLA complexes, and the acquired Ags could be efficiently recognized on pDCs by tumor-specific CD8(+) T cells. Remarkably, pDCs isolated from human colon cancer tissues displayed a strong surface expression of epithelial cell adhesion molecule, indicating that the exchange of exogenous Ags between pDCs and tumor cells also can occur in vivo. These data demonstrate that pDCs are well suited to acquire membrane patches from contiguous tumor cells by a cell-to-cell contact-dependent mechanism that closely resembles "trogocytosis." This phenomenon may allow pDCs to proficiently present tumor cell-derived Ags, despite limited properties of endophagocytosis.

摘要

浆细胞样树突状细胞 (pDCs) 在呈递肿瘤细胞 Ag 方面的潜在贡献尚不清楚,并且关于 pDCs 摄取细胞来源的颗粒性 Ag 并将其交叉呈递给 MHC Ⅰ类限制性 T 淋巴细胞的能力存在一些争议。在这项研究中,我们表明,尽管人 pDCs 通过吞噬作用摄取细胞膜片段的效率不高,但它们可以有效地从不同组织类型的癌细胞中获得膜斑和相关分子。膜斑向 pDCs 的转移发生在很短的时间内,需要细胞间接触。膜转移还包括完整的 HLA 复合物,并且获得的 Ag 可以被肿瘤特异性 CD8(+) T 细胞有效地识别。值得注意的是,从人结肠癌组织中分离出的 pDCs 表面强烈表达上皮细胞黏附分子,表明 pDCs 和肿瘤细胞之间也可以发生外源性 Ag 的交换。这些数据表明,pDCs 非常适合通过类似于“胞饮作用”的细胞间接触依赖性机制从相邻的肿瘤细胞中获取膜斑。这种现象可能允许 pDCs 有效地呈递肿瘤细胞衍生的 Ag,尽管内吞作用的特性有限。

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