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Spatial interplay of lymphocytes and fibroblasts in estrogen receptor-positive HER2-negative breast cancer
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Nederlof, I., Hajizadeh, S., Sobhani, F., Raza, Shan-e-Ahmed, AbdulJabbar, K., Harkes, R., van de Vijver, M. J., Salgado, R., Desmedt, C., Kok, M., Yuan, Y. and Horlings, H. M. (2022) Spatial interplay of lymphocytes and fibroblasts in estrogen receptor-positive HER2-negative breast cancer. npj Breast Cancer, 8 (1). 56. doi:10.1038/s41523-022-00416-y ISSN 2374-4677.
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WRAP-spatial-interplay-lymphocytes-fibroblasts-estrogen-receptor-positive-HER2-negative breast cancer-Raza-2022.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (4081Kb) | Preview |
Official URL: https://doi.org/10.1038/s41523-022-00416-y
Abstract
In estrogen-receptor-positive, HER2-negative (ER+HER2−) breast cancer, higher levels of tumor infiltrating lymphocytes (TILs) are often associated with a poor prognosis and this phenomenon is still poorly understood. Fibroblasts represent one of the most frequent cells in breast cancer and harbor immunomodulatory capabilities. Here, we evaluate the molecular and clinical impact of the spatial patterns of TILs and fibroblast in ER+HER2− breast cancer. We used a deep neural network to locate and identify tumor, TILs, and fibroblasts on hematoxylin and eosin-stained slides from 179 ER+HER2− breast tumors (ICGC cohort) together with a new density estimation analysis to measure the spatial patterns. We clustered tumors based on their spatial patterns and gene set enrichment analysis was performed to study their molecular characteristics. We independently assessed the spatial patterns in a second cohort of ER+HER2− breast cancer (N = 630, METABRIC) and studied their prognostic value. The spatial integration of fibroblasts, TILs, and tumor cells leads to a new reproducible spatial classification of ER+HER2− breast cancer and is linked to inflammation, fibroblast meddling, or immunosuppression. ER+HER2− patients with high TIL did not have a significant improved overall survival (HR = 0.76, P = 0.212), except when they had received chemotherapy (HR = 0.447). A poorer survival was observed for patients with high fibroblasts that did not show a high level of TILs (HR = 1.661, P = 0.0303). Especially spatial mixing of fibroblasts and TILs was associated with a good prognosis (HR = 0.464, P = 0.013). Our findings demonstrate a reproducible pipeline for the spatial profiling of TILs and fibroblasts in ER+HER2− breast cancer and suggest that this spatial interplay holds a decisive role in their cancer-immune interactions.
| Item Type: | Journal Article | ||||||
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| Subjects: | Q Science > QP Physiology R Medicine > RC Internal medicine |
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| Divisions: | Faculty of Science, Engineering and Medicine > Science > Computer Science | ||||||
| SWORD Depositor: | Library Publications Router | ||||||
| Library of Congress Subject Headings (LCSH): | Breast -- Cancer, Breast -- Cancer -- Diagnosis -- Data processing, Tumors -- Growth -- Data processing, Lymphocytes, Cancer cells -- Growth -- Data processing, Fibroblasts, Diagnostic imaging | ||||||
| Journal or Publication Title: | npj Breast Cancer | ||||||
| Publisher: | Springer | ||||||
| ISSN: | 2374-4677 | ||||||
| Official Date: | 28 April 2022 | ||||||
| Dates: |
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| Volume: | 8 | ||||||
| Number: | 1 | ||||||
| Article Number: | 56 | ||||||
| DOI: | 10.1038/s41523-022-00416-y | ||||||
| Status: | Peer Reviewed | ||||||
| Publication Status: | Published | ||||||
| Access rights to Published version: | Open Access (Creative Commons) | ||||||
| Date of first compliant deposit: | 20 May 2022 | ||||||
| Date of first compliant Open Access: | 23 May 2022 | ||||||
| RIOXX Funder/Project Grant: |
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