IFI30 promotes tumor-associated macrophage infiltration via activation of the ATF3-CCL5 axis in breast cancer

作者：Liwen Ren, Yihui Yang, Li Wan, Xiangjin Zheng, Jinyi Liu, Sha Li, Yang Hong, Yizhi Zhang, Hongquan Wang, Guanhua Du, Xifu Wang, Jinhua Wang · 发表于：The Innovation · 年份：2025 · DOI：10.1016/j.xinn.2025.101005 · 被引用次数：1 · 研究领域：Immune cells in cancer、Immune Cell Function and Interaction、Phagocytosis and Immune Regulation

Immunotherapy has transformed cancer treatment, but its effectiveness in breast cancer remains suboptimal. Tumor-associated macrophages (TAMs), a key component of the tumor microenvironment (TME), contribute significantly to immune evasion. In this study, we identified gamma-interferon-inducible lysosomal thiol reductase (IFI30) as a critical regulator of TAM function in breast cancer. IFI30 expression is upregulated in breast cancer via enhanced Histone 3 lysine 27 acetylation (H3K27ac) modification and promotes tumor progression and metastasis in an immune-dependent manner. Mechanistically, IFI30 in breast cancer cells recruits TAMs by activating the ATF3-CCL5 axis. Within macrophages, it promotes M2-like polarization and PD-L1 upregulation, fostering an immunosuppressive TME. Our findings established IFI30 as a promising therapeutic target for disrupting TAM-mediated immune suppression and enhancing breast cancer immunotherapy.