Spatial Structure of Tumor and Immune Cells Shape Outcomes in ER-positive-HER2-negative and Triple-negative Breast Cancer
Nederlof, I.; Hajizadeh, S.; Harkes, R.; Andrade Barbosa, B.; de Maaker, M.; Hofland, I.; Peters, D.; Elens, R.; Broeks, A.; van Werkhoven, E.; Kim, Y.; Ijsselstein, M.; de Miranda, N. F. C. C.; Bosma, S.; Visser, N. C. M.; Snijders, M. L. H.; Sanders, J.; Salgado, R.; Poortmans, P.; Scholten, A.; Boersma, L. J.; Kok, M.; Bartelink, H.; Van De Vijver, M. J.; Horlings, H. M.
Show abstract
Immune infiltration is prognostic in triple-negative breast cancer (TNBC), but its role in ER/HER2- disease remains unclear, and conventional scoring may overlook spatial context. We analyzed tumors from 1,037 women [≤]50 years in the Young Boost Trial (NCT00212121), integrating centralized pathology review, deep learning-based spatial profiling of whole-slide H&E, and multiplex immunophenotyping. In TNBC, stromal tumor-infiltrating lymphocytes (sTILs) were robustly prognostic, independent of clinicopathologic features, confirming immune burden as the dominant signal. By contrast, in ER/HER2- cancers, sTILs were protective only in low-grade tumors and lost significance when architectural features were considered. Instead, grade, lymphovascular invasion, central sclerosis, and spatial separation of lymphocytes and tumor cells carried stronger independent prognostic value. These findings highlight subtype-specific prognostic biology: in TNBC, immune density alone captures outcome, whereas in ER/HER2- disease, the interplay between immune infiltrates and tumor architecture governs prognostic associations.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Multiplexed RNA-FISH-guided Laser Capture Microdissection RNA Sequencing Improves Breast Cancer Molecular Subtyping, Prognostic Classification, and Predicts Response to Antibody Drug Conjugates 97%
- CD39+PD-1+CD8+ T cells mediate metastatic dormancy in breast cancer 97%
- Combinatorial immunotherapies overcome MYC-driven immune evasion 96%
Similar papers in this journal
- The breast pre-cancer atlas illustrates the molecular and micro-environmental diversity of ductal carcinoma in situ 96%
- The clinical and molecular significance associated with STING signaling in estrogen receptor-positive early breast cancer 96%
- Normal Breast Tissue (NBT)-Classifiers: Advancing Compartment Classification in Normal Breast Histology 95%
Similar papers in this journal
- Multimodal Spatial Profiling Reveals Immune Suppression and Microenvironment Remodeling in Fallopian Tube Precursors to High-Grade Serous Ovarian Carcinoma 97%
- Single cell view of tumor microenvironment gradients in pleural mesothelioma 95%
- Generation of a biliary tract cancer cell line atlas reveals molecular subtypes and therapeutic targets 95%
Similar papers in this journal
- Genome-wide identification and analysis of prognostic features in human cancers 95%
- Distinct mutational processes shape selection of MHC class I and class II mutations across primary and metastatic tumors 95%
- Evolution of chromosome arm aberrations in breast cancer through genetic network rewiring 95%
Similar papers in this journal
- Immune and malignant cell phenotypes of ovarian cancer are determined by distinct mutational processes 96%
- Heterogeneity in PHGDH protein expression potentiates cancer cell dissemination and metastasis 95%
- Functional interrogation uncovers a critical role for a high-plasticity cell state in lung adenocarcinoma 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.