Predicting immune responsiveness in ER-positive breast cancer for personalized therapy: a population-based study
Abstract 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 respon...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-07-01
|
| Series: | npj Precision Oncology |
| Online Access: | https://doi.org/10.1038/s41698-025-01035-z |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849333917999431680 |
|---|---|
| author | Axel Stenmark Tullberg Sara Woxlin Filippa Sjölin Ella Ittner Anikò Kovàcs Khalil Helou Erik Holmberg Per Karlsson |
| author_facet | Axel Stenmark Tullberg Sara Woxlin Filippa Sjölin Ella Ittner Anikò Kovàcs Khalil Helou Erik Holmberg Per Karlsson |
| author_sort | Axel Stenmark Tullberg |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-17d842a43b304b9e934d72f609e46811 |
| institution | Kabale University |
| issn | 2397-768X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Precision Oncology |
| spelling | doaj-art-17d842a43b304b9e934d72f609e468112025-08-20T03:45:44ZengNature Portfolionpj Precision Oncology2397-768X2025-07-019111210.1038/s41698-025-01035-zPredicting immune responsiveness in ER-positive breast cancer for personalized therapy: a population-based studyAxel Stenmark Tullberg0Sara Woxlin1Filippa Sjölin2Ella Ittner3Anikò Kovàcs4Khalil Helou5Erik Holmberg6Per Karlsson7Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University HospitalDepartment of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University HospitalDepartment of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University HospitalDepartment of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University HospitalDepartment of Clinical Pathology, Sahlgrenska University HospitalDepartment of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University HospitalDepartment of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University HospitalDepartment of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University HospitalAbstract 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.https://doi.org/10.1038/s41698-025-01035-z |
| spellingShingle | Axel Stenmark Tullberg Sara Woxlin Filippa Sjölin Ella Ittner Anikò Kovàcs Khalil Helou Erik Holmberg Per Karlsson Predicting immune responsiveness in ER-positive breast cancer for personalized therapy: a population-based study npj Precision Oncology |
| title | Predicting immune responsiveness in ER-positive breast cancer for personalized therapy: a population-based study |
| title_full | Predicting immune responsiveness in ER-positive breast cancer for personalized therapy: a population-based study |
| title_fullStr | Predicting immune responsiveness in ER-positive breast cancer for personalized therapy: a population-based study |
| title_full_unstemmed | Predicting immune responsiveness in ER-positive breast cancer for personalized therapy: a population-based study |
| title_short | Predicting immune responsiveness in ER-positive breast cancer for personalized therapy: a population-based study |
| title_sort | predicting immune responsiveness in er positive breast cancer for personalized therapy a population based study |
| url | https://doi.org/10.1038/s41698-025-01035-z |
| work_keys_str_mv | AT axelstenmarktullberg predictingimmuneresponsivenessinerpositivebreastcancerforpersonalizedtherapyapopulationbasedstudy AT sarawoxlin predictingimmuneresponsivenessinerpositivebreastcancerforpersonalizedtherapyapopulationbasedstudy AT filippasjolin predictingimmuneresponsivenessinerpositivebreastcancerforpersonalizedtherapyapopulationbasedstudy AT ellaittner predictingimmuneresponsivenessinerpositivebreastcancerforpersonalizedtherapyapopulationbasedstudy AT anikokovacs predictingimmuneresponsivenessinerpositivebreastcancerforpersonalizedtherapyapopulationbasedstudy AT khalilhelou predictingimmuneresponsivenessinerpositivebreastcancerforpersonalizedtherapyapopulationbasedstudy AT erikholmberg predictingimmuneresponsivenessinerpositivebreastcancerforpersonalizedtherapyapopulationbasedstudy AT perkarlsson predictingimmuneresponsivenessinerpositivebreastcancerforpersonalizedtherapyapopulationbasedstudy |