Immunological and Prognostic Profiling of Triple-Negative Breast Cancer Based on Single-Cell and Bulk RNA Sequencing of T-Cell Exhaustion

Introduction Triple-Negative Breast Cancer (TNBC) is a subtype of breast cancer characterized by the absence of estrogen receptors, progesterone receptors, and HER2 expression, accounting for approximately 15% of all breast cancer cases. TNBC is associated with poor prognosis and lacks effective targeted therapies. T cell exhaustion (TEX) refers to the functional decline of T cells within the tumor microenvironment, which adversely affects immune responses. This study investigates the role of TEX in TNBC and its relationship with patient prognosis. The objective of this research is to evaluate the impact of TEX characteristics on the response to immunotherapy in TNBC patients through single-cell RNA sequencing and various bioinformatics analyses, aiming to identify potential biomarkers and therapeutic targets. Methods We performed a comprehensive analysis of the GSE161529 dataset using 10× scRNA-seq, identifying 12,477 high-quality cells and seven distinct cell subpopulations. Differential expression analysis and co-expression network construction revealed 154 candidate TEX-related genes, from which five prognostically significant genes were selected to construct a risk scoring model. Results Our findings indicate that TEX characteristics are crucial for prognostic assessment in TNBC patients, with significant correlations between risk scores and tumor-infiltrating immune cells. High-risk patients exhibited elevated expression levels of immune checkpoint genes, suggesting potential implications for immunotherapy. Conclusions This study underscores the clinical significance of TEX features in TNBC prognosis and highlights the urgent need for therapeutic strategies targeting TEX to improve patient outcomes.