Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Front Immunol. 2022 Jun 30;13:923481. doi: 10.3389/fimmu.2022.923481. eCollection 2022.
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. 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.
三阴性乳腺癌（TNBC）仍然是最差的分子亚型，因为其具有高度异质性和缺乏有效的治疗靶点。在这里，我们使用来自公共数据库和我们的队列的 scRNA-seq 和批量 RNA-seq 数据，研究了 TNBC 的肿瘤和免疫微环境异质性。巨噬细胞亚群在肿瘤免疫微环境（TIME）中占据了很高的比例，M1 巨噬细胞与更好的临床结局相关。此外，包括 IFI35、PSMB9 和 SAMD9L 在内的三个标记基因与 M1 巨噬细胞密切相关。具体来说，IFI35 与巨噬细胞的激活、趋化和迁移呈正相关。此外，IFI35 高表达的患者预后更好。随后的研究表明，IFI35 在巨噬细胞的 M1 亚型分化过程中被上调。总之，我们的数据表明，IFI35 可能是一个有前途的新靶点，可以帮助重塑巨噬细胞向 M1 亚型极化，从而发挥抗肿瘤作用。
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