Resolving tumor microenvironment heterogeneity to forecast immunotherapy response in triple-negative breast cancer through multi-scale analysis.

ABSTRACT:

Background

Immunotherapy has been used in the clinical management of TNBC. While BRCA1 mutations are associated with immunotherapy response, the therapeutic outcomes in TNBC patients are not promising.

Methods

This study integrated spatial, single-cell, and bulk RNA-seq data to explore the role of BRCA1 in reshaping the TNBC microenvironment. Through multi-scale analysis, phenotype changes and potential biomarkers in cancer-associated fibroblasts (CAF) were identified. To validate these findings at the protein level, we employed high-resolution, label-free proteomics sequencing in our in-house cohort, providing critical real-world validation. A predictive system for response to ICIs was constructed through the step-by-step machine learning pipeline.

Results

Compared t

SUBMITTER: Sun S 

PROVIDER: S-EPMC12401915 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature