CD169 identifies an anti-tumour macrophage subpopulation in human hepatocellular carcinoma
CD169 identifies an anti-tumour macrophage subpopulation in human hepatocellular carcinoma
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CD169 鉴定人肝细胞癌中的抗肿瘤巨噬细胞亚群
DOI：
10.1002/path.4720
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发表时间：
2016-06-01
影响因子：
7.3
通讯作者：
Zheng, Limin
中科院分区：
文献类型：
--
作者：
Zhang, Yi;Li, Jin-Qing;Zheng, Limin
巨噬细胞是大多数实体瘤的主要组成部分，可以发挥抗肿瘤和促肿瘤功能。虽然巨噬细胞的免疫抑制/促肿瘤作用已被广泛研究，但对人类中具有潜在抗肿瘤特性的巨噬细胞亚群知之甚少。在本研究中，在人肝细胞癌组织中鉴定了具有相对高的HLA-DR和CD 86表达水平的CD 169（+）巨噬细胞群体。癌巢内表达CD 169的巨噬细胞的频率显著低于配对的非肿瘤区域。体外实验表明，在抗CD 3刺激的存在下，CD 169（+）巨噬细胞可以以CD 169分子依赖的方式显著增强CD 8（+）T细胞的增殖、细胞毒性和细胞因子产生能力。自分泌TGF-β 1由肿瘤刺激的巨噬细胞产生的CD 169参与了这些细胞上CD 169表达的下调。此外，肿瘤组织中CD 169（+）巨噬细胞的积累与疾病进展呈负相关，并预测肝细胞癌患者的良好生存，这与总CD 68（+）巨噬细胞的趋势相反。因此，CD 169可能作为细胞毒性T细胞活化的共刺激分子，并且可以在人肝细胞癌组织中定义具有潜在抗肿瘤特性的肿瘤浸润性巨噬细胞群体。版权所有（C）2016大不列颠及爱尔兰病理学会。由John Wiley & Sons有限公司出版
Macrophages are a major component of most solid tumours and can exert both anti-and pro-tumourigenic functions. Although the immunosuppressive/pro-tumour roles of macrophages have been widely examined, significantly less is known about macrophage subpopulations that have potential anti-tumour properties in humans. In the present study, a population of CD169(+) macrophages with relatively high expression levels of HLA-DR and CD86 was identified in human hepatocellular carcinoma tissues. The frequency of CD169-expressing macrophages within cancer nests was significantly lower than that found in paired non-tumour areas. In vitro experiments revealed that in the presence of anti-CD3 stimulation, CD169(+) macrophages could significantly enhance the proliferation, cytotoxicity, and cytokine production capacity of CD8(+) T cells in a CD169 molecule-dependent manner. Autocrine TGF-.. produced by tumour-stimulated macrophages was involved in the down-regulation of CD169 expression on these cells. Moreover, the accumulation of CD169(+) macrophages in tumour tissues was negatively associated with disease progression and predicted favourable survival in hepatocellular carcinoma patients, which was in contrast to the trend observed for total CD68(+) macrophages. Therefore, CD169 might act as a co-stimulatory molecule for cytotoxic T-cell activation, and could define a population of tumour-infiltrating macrophages with potential anti-tumour properties in human hepatocellular carcinoma tissues. Copyright (C) 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.