ArticleBreast cancer research : BCR2026
Epithelial-mesenchymal transition is associated with altered immune composition and cytotoxic function in triple-negative breast cancer.
Article in Breast cancer research : BCR, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundEpithelial-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.
methodsTo 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.
resultsTumors 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) cells similarly demonstrated progressive functional suppression, marked by reduced expression of cytotoxic molecules and the downregulation of specific effector pathways.
conclusionsThese findings reveal that EMT is associated with immune cell recruitment and function in a graded manner, providing a rationale for integrating EMT phenotyping into therapeutic strategies to overcome immune resistance in breast cancer.
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