Mapping the Tumor Microenvironment in TNBC and Deep Exploration for M1 Macrophages-Associated Prognostic Genes.
Mapping the Tumor Microenvironment in TNBC and Deep Exploration for M1 Macrophages-Associated Prognostic Genes.
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DOI：
10.3389/fimmu.2022.923481
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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由于高度的异质性和缺乏有效的治疗靶点，三阴性乳腺癌(TNBC)仍然是最糟糕的分子亚型。在这里，我们使用来自公共数据库和我们的队列的scRNA-seq和大量RNA-seq数据来研究TNBC的肿瘤和免疫微环境的异质性。巨噬细胞亚群在肿瘤免疫微环境(TIME)中所占比例较高，而M1巨噬细胞与较好的临床预后相关。此外，IFI35、PSMB9和SAMD9L三个标记基因与M1巨噬细胞密切相关。具体地说，IFI35与巨噬细胞的激活、趋化和迁移正相关。此外，IFI35高表达的患者预后较好。随后的体外研究表明，在巨噬细胞M1亚型分化过程中，IFI35表达上调。综上所述，我们的数据表明，IFI35可能是一个有希望的新靶点，有助于重塑巨噬细胞向M1亚型的极化，从而发挥抗肿瘤作用。
Triple negative breast cancer (TNBC) remains the worst molecular subtype due to high heterogeneity and lack of effective therapeutic targets. Here we investigated the tumor and immune microenvironment heterogeneity of TNBC using scRNA-seq and bulk RNA-seq data from public databases and our cohort. Macrophage subpopulations accounted for a high proportion of tumor immune microenvironment (TIME), and M1 macrophages were associated with better clinical outcomes. Furthermore, three maker genes including IFI35, PSMB9, and SAMD9L showed a close connection with M1 macrophages. Specifically, IFI35 was positively associated with macrophage activation, chemotaxis, and migration. Also, patients with high IFI35 expression had a better prognosis. In vitro studies subsequently demonstrated that IFI35 was upregulated during the M1 subtype differentiation of macrophages. In summary, our data suggested that IFI35 maybe a promising novel target that helps to reshape macrophage polarization towards the M1 subtype for anti-tumor effects.
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