Epithelial-mesenchymal transition is associated with altered immune composition and cytotoxic function in triple-negative breast cancer

作者：Hanxu Lu, Meisam Bagheri, Fred Kolling, Lucas A. Salas, Xiaofeng Wang, Todd W. Miller, Diwakar R. Pattabiraman, Brock C. Christensen · 发表于：Breast Cancer Research · 年份：2026 · DOI：10.1186/s13058-026-02309-5 · 研究领域：Cancer Cells and Metastasis、Cancer-related molecular mechanisms research

BACKGROUND: Epithelial-mesenchymal transition (EMT) is a dynamic process that contributes to breast cancer progression, metastasis, and therapy resistance. EMT also influences the tumor immune microenvironment, shaping immune cell infiltration and function. Although the immunological features of fully epithelial or fully mesenchymal tumor states have been characterized, the immune landscape associated with intermediate or partial EMT states remains poorly understood. METHODS: To examine the relationship between EMT progression and immune cell composition and function, we established five single-cell-derived clonal populations from the triple-negative 4T1 mouse mammary tumor cell line, representing a spectrum of EMT phenotypes, and analyzed tumors derived from these clones using single-cell RNA sequencing. RESULTS: Tumors derived from these clones retained their relative EMT states in vivo, and EMT progression was associated with a graded reduction in tumor immunogenicity, accompanied by alterations in immune cell composition and function. Along the EMT spectrum, tumor cells exhibited progressive downregulation of major histocompatibility complex (MHC) class I and II gene expression, along with decreased infiltration of cytotoxic CD8+ T cells and reduced expression of key effector and trafficking genes (Gzmb, Ccr5, Cxcr6). B cell composition also shifted, with decreased frequencies of IgG1-producing plasma cells and an enrichment of regulatory-like B cells. Natural killer (NK)...