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CD169 鉴定出人类肝癌中的抗肿瘤巨噬细胞亚群。

CD169 identifies an anti-tumour macrophage subpopulation in human hepatocellular carcinoma.

机构信息

Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou, PR China.

Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, PR China.

出版信息

J Pathol. 2016 Jun;239(2):231-41. doi: 10.1002/path.4720. Epub 2016 Apr 27.

Abstract

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-β 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 © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

摘要

巨噬细胞是大多数实体瘤的主要组成部分,可发挥抑瘤和促瘤双重作用。虽然巨噬细胞的免疫抑制/促瘤作用已被广泛研究,但对于具有人类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出一种 CD169(+)巨噬细胞亚群,其 HLA-DR 和 CD86 的表达水平相对较高。癌巢内表达 CD169 的巨噬细胞的频率明显低于配对非肿瘤区域。体外实验表明,在抗 CD3 刺激下,CD169(+)巨噬细胞可显著增强 CD8(+)T 细胞的增殖、细胞毒性和细胞因子产生能力,这是一种依赖于 CD169 分子的方式。肿瘤刺激的巨噬细胞产生的自分泌 TGF-β 参与了这些细胞上 CD169 表达的下调。此外,肿瘤组织中 CD169(+)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生存预后良好,与总 CD68(+)巨噬细胞的趋势相反。因此,CD169 可能作为细胞毒性 T 细胞激活的共刺激分子发挥作用,并可定义人类肝细胞癌组织中具有潜在抗肿瘤特性的浸润性巨噬细胞群体。版权所有 © 2016 英国和爱尔兰病理学学会。由 John Wiley & Sons, Ltd. 出版。

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