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Updated: Feb 27, 2026
Three-dimensional Co-culture Model for Tumor-stromal Interaction
Published on: February 2, 2015
Identification of Interacting Stromal Axes in Triple-Negative Breast Cancer
Sadiq M I Saleh1,2,3, Nicholas Bertos1, Tina Gruosso1
1Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada.
Abstract:
Triple-negative breast cancer (TNBC) is a molecularly heterogeneous cancer that is difficult to treat. Despite the role it may play in tumor progression and response to therapy, microenvironmental (stromal) heterogeneity in TNBC has not been well characterized. To address this challenge, we investigated the transcriptome of tumor-associated stroma isolated from TNBC (n = 57). We identified four stromal axes enriched for T cells (T), B cells (B), epithelial markers (E), or desmoplasia (D). Our analysis method (STROMA4) assigns a score along each stromal axis for each patient and then combined the axis scores to subtype patients. Analysis of these subtypes revealed that prognostic capacity of the B, T, and E scores was governed by the D score. When compared with a previously published TNBC subtyping scheme, the STROMA4 method better captured tumor heterogeneity and predicted patient benefit from therapy with increased sensitivity. This approach produces a simple ontology that captures TNBC heterogeneity and informs how tumor-associated properties interact to affect prognosis. Cancer Res; 77(17); 4673-83. ©2017 AACR.
Insights
This study characterizes tumor microenvironment heterogeneity in triple-negative breast cancer (TNBC). A new method, STROMA4, identifies stromal subtypes that better predict prognosis and therapy response in TNBC patients.
Area of Science:
- Oncology
- Cancer Biology
- Immunology
Background:
- Triple-negative breast cancer (TNBC) is a heterogeneous and challenging malignancy.
- The tumor microenvironment, particularly stromal heterogeneity, is crucial for TNBC progression and treatment response but remains poorly understood.
Purpose of the Study:
- To investigate the transcriptome of tumor-associated stroma in TNBC.
- To develop a novel method for characterizing stromal heterogeneity and its impact on prognosis and therapy.
Main Methods:
- Analysis of tumor-associated stroma transcriptomes from 57 TNBC patients.
- Development of the STROMA4 analysis method to identify four stromal axes (T cells, B cells, epithelial markers, desmoplasia).
- Subtyping patients based on STROMA4 scores and evaluating prognostic capacity.
Main Results:
- Identification of four distinct stromal axes: T cells (T), B cells (B), epithelial markers (E), and desmoplasia (D).
- The prognostic significance of B, T, and E scores was modulated by the D score.
- The STROMA4 method demonstrated superior capture of TNBC heterogeneity and prediction of therapy benefit compared to existing schemes.
Conclusions:
- The STROMA4 method provides a robust approach to understanding TNBC stromal heterogeneity.
- This subtyping strategy improves prediction of patient prognosis and response to therapy.
- The findings offer a new framework for analyzing tumor-associated properties and their interactions in TNBC.
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