文章：

SIRPα表达定义了滤泡性淋巴瘤中具有不同功能和预后影响的肿瘤内单核细胞/巨噬细胞亚群

SIRPα expression delineates subsets of intratumoral monocyte/macrophages with different functional and prognostic impact in follicular lymphoma

原文发布日期：2019-10-14

DOI: 10.1038/s41408-019-0246-0

类型: Article

开放获取: 是

英文摘要：

Signal regulatory protein-α (SIRPα) is a key member of the “do-not-eat-me” signaling pathway, but its biological role and clinical relevance in B-cell NHL is relatively unknown. Using biopsy specimens from follicular lymphoma (FL), we identified three subsets (CD14+SIRPαhi, CD14−SIRPαlow, and CD14−SIRPαneg) of monocyte/macrophages (Mo/MΦ) based on CD14 and SIRPα expression. CD14+SIRPαhi cells expressed common Mo/MΦ markers; exhibited characteristic differentiation, migration, and phagocytosis; and suppressed T-cell function. CD14−SIRPαlow cells expressed fewer typical Mo/MΦ markers; migrated less and phagocytosed tumor cells less efficiently; and stimulated rather than suppressed T-cell function. Interestingly, the CD14−SIRPαneg subset expressed distinct Mo/MΦ markers compared to the other two subsets; had limited ability to migrate and phagocytose; but stimulated T-cell function. When using SIRPα-Fc to block the interaction between SIRPα and CD47, alone or in combination with rituximab, phagocytosis of tumor cells was differentially increased in the three Mo/MΦ subsets. Clinically, increased numbers of CD14+SIRPαhi cells were associated with an inferior survival in FL. In contrast, increased numbers of the CD14−SIRPαlow subset appeared to correlate with a better survival. Taken together, our results show that SIRPα expression delineates unique subsets of intratumoral Mo/MΦs with differing prognostic importance.
 

摘要翻译： 

信号调节蛋白α（SIRPα）是“别吃我”信号通路的关键成员，但其在B细胞非霍奇金淋巴瘤（NHL）中的生物学作用及临床相关性尚不明确。通过分析滤泡性淋巴瘤（FL）的活检标本，我们根据CD14和SIRPα的表达水平将单核细胞/巨噬细胞（Mo/MΦ）划分为三个亚群：CD14+SIRPαhi、CD14−SIRPαlow和CD14−SIRPαneg。CD14+SIRPαhi细胞表达常见的Mo/MΦ标志物，具有典型的分化、迁移和吞噬特征，并能抑制T细胞功能；CD14−SIRPαlow细胞表达的典型Mo/MΦ标志物较少，迁移能力和对肿瘤细胞的吞噬效率较低，且能刺激而非抑制T细胞功能；值得注意的是，CD14−SIRPαneg亚群表达的Mo/MΦ标志物与前两个亚群不同，其迁移和吞噬能力有限，但可激活T细胞功能。当使用SIRPα-Fc阻断SIRPα与CD47的相互作用（单独或联合利妥昔单抗）时，三个Mo/MΦ亚群对肿瘤细胞的吞噬作用均呈现差异性增强。临床分析显示，FL组织中CD14+SIRPαhi细胞数量增加与患者较短生存期相关，而CD14−SIRPαlow亚群数量增加则与较好预后相关。综上，SIRPα的表达可界定肿瘤内Mo/MΦ的不同功能亚群，这些亚群具有差异化的预后价值。

原文链接：

SIRPα expression delineates subsets of intratumoral monocyte/macrophages with different functional and prognostic impact in follicular lymphoma