Predicting immune responsiveness in ER-positive breast cancer for personalized therapy: a population-based study.
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Stenmark Tullberg A, Woxlin S, Sjölin F, Ittner E, Kovàcs A, Helou K, Holmberg E, Karlsson P
NPJ Precis Oncol 9 (1) 250 [2025-07-23; online 2025-07-23]
The immune system's role in estrogen receptor (ER)-positive breast cancer is poorly understood. A population-based cohort of 428 breast cancer patients with clinical and molecular data was analyzed to assess how immune biomarkers can inform treatment decisions. Tumor-intrinsic immune responsiveness and local immune infiltration were quantified, and epithelial cell states were derived using EcoTyper. The interaction between ProliferativeIndex and Immunescore predicted risk of local recurrence in ER-positive tumors (HR 0.56, 95% CI 0.36-0.88, p = 0.012). EcoTyper identified two epithelial cell states, S04 and S05, with distinct immunomodulatory properties. S04 tumors showed higher proliferation, enrichment for M1 macrophages, CD8 effector T-cells, and plasma cells, alongside hypomethylation of immune-related pathways and hypermethylation of the PI3K signaling pathway. In contrast, S05-enriched tumors were associated with fibroblast activation, immune exclusion, and enrichment for glycosylation-related pathways. These findings suggest that epithelial cell states shape immune responsiveness in ER-positive breast cancer and may inform biomarker-driven treatment strategies.
NGI Uppsala (SNP&SEQ Technology Platform) [Service]
National Genomics Infrastructure [Service]
PubMed 40702082
DOI 10.1038/s41698-025-01035-z
Crossref 10.1038/s41698-025-01035-z
pmc: PMC12287262
pii: 10.1038/s41698-025-01035-z