The role of tumor microenvironment and immune cell crosstalk in triple-negative breast cancer (TNBC): Emerging therapeutic opportunities

Abstract

Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by its lack of estrogen, progesterone, and HER2 receptors, leading to limited treatment options and poor prognosis. This review synthesizes current research on the tumor microenvironment (TME) and immune cell crosstalk in TNBC to identify emerging therapeutic opportunities. The TME in TNBC is a complex ecosystem comprising immune cells, fibroblasts, and extracellular matrix components, which significantly influence tumor growth and metastasis. Single-cell RNA sequencing reveals T-cell heterogeneity and identifies prognostic genes. Regulatory T cells (Tregs) play a key role in immunosuppression, with thymidine kinase-1 (TK1) identified as a potential therapeutic target. MUC1-C and CXCL9 modulate the TME, impacting T-cell depletion and macrophage differentiation. Spatial analysis highlights the importance of cell-to-cell interactions in predicting recurrence. Epithelial-mesenchymal transition (EMT) and thermogenesis also influence the TME, while epigenetic modifications, such as HDAC inhibition, can induce pyroptosis and enhance immune cell recruitment. Integrating genomic information with TME analysis is crucial for developing personalized treatments, considering racial disparities in immune infiltration. Emerging therapies targeting immune checkpoints, modulating Treg activity, and inducing pyroptosis hold promise for improving TNBC patient outcomes. Future research should focus on multi-omics data, spatial transcriptomics, and patient-derived models to refine therapeutic interventions.

Keywords: (ADC); (AI); (MDSCs); (PARPi); (TME); AR/Scr/Pl3-K; Anti-androgen therapies; Antibody-drug conjugate; Artificial intelligence; Immunotherapy; Myeloid-derived suppressor cells; PARP inhibitors; Prognostic markers; Targeted therapy; Tumor microenvironment.