The tumor microenvironment and triple-negative breast cancer aggressiveness: shedding light on mechanisms and targeting

Abstract

Introduction: In contrast to other breast cancer subtypes, there are currently limited options of targeted therapies for triple-negative breast cancer (TNBC). Immense research has demonstrated that not only cancer cells but also stromal cells and immune cells in the tumor microenvironment (TME) play significant roles in the progression of TNBC. It is thus critical to understand the components of the TME of TNBC and the interactions between the various cell populations.

Areas covered: The components of the TME of TNBC identified by single-cell technologies are reviewed. Furthermore, the molecular interactions between the cells and the potential therapeutic targets contributing to the progression of TNBC are discussed.

Expert opinion: Single-cell omics studies have contributed to the classification of cells in the TME and the identification of important cell types involved in the progression and the treatment of the tumor. The interactions between cancer cells and stromal cells/immune cells in the TME have led to the discovery of potential therapeutic targets. Experimental data with spatial and temporal resolution will further boost the understanding of the TME of TNBC.

Keywords: immunotherapy; single-cell analysis; triple-negative breast cancer; tumor microenvironment.

Figure 1.

Subpopulations of lymphocytes in the TME of TNBC. Cells shown in the figure represent the major cell types of lymphocytes in TNBC. ScRNA-seq analyses have revealed that lymphocytes show a continuous phenotype. Although the classification methods and the nomenclature vary between studies, each cell type may be further classified based on their transcriptional characteristics. For T cells, features such as T cell activation, terminal differentiation, and hypoxia may be used to differentiate the cells.

Figure 2.

Subpopulations of myeloid cells in the TME of TNBC. Cells shown in the figure represent the major cell types of myeloid cells in TNBC. ScRNA-seq analyses have revealed that myeloid cells show a continuous phenotype. Although the classification methods and the nomenclature vary between studies, each cell type may be further classified based on their transcriptional characteristics. Features such as monocyte activation, TAM activation, and pDC component may be used to differentiate the cells.