Mapping Breast Cancer Microenvironment Through Single-Cell Omics

Abstract

Breast cancer development and progression rely not only on the proliferation of neoplastic cells but also on the significant heterogeneity in the surrounding tumor microenvironment. Its unique microenvironment, including tumor-infiltrating lymphocytes, complex myeloid cells, lipid-associated macrophages, cancer-associated fibroblasts (CAFs), and other molecules that promote the growth and migration of tumor cells, has been shown to play a crucial role in the occurrence, growth, and metastasis of breast cancer. However, a detailed understanding of the complex microenvironment in breast cancer remains largely unknown. The unique pattern of breast cancer microenvironment cells has been poorly studied, and neither has the supportive role of these cells in pathogenesis been assessed. Single-cell multiomics biotechnology, especially single-cell RNA sequencing (scRNA-seq) reveals single-cell expression levels at much higher resolution, finely dissecting the molecular characteristics of tumor microenvironment. Here, we review the recent literature on breast cancer microenvironment, focusing on scRNA-seq studies and analyzing heterogeneity and spatial location of different cells, including T and B cells, macrophages/monocytes, neutrophils, and stromal cells. This review aims to provide a more comprehensive perception of breast cancer microenvironment and annotation for their clinical classification, diagnosis, and treatment. Furthermore, we discuss the impact of novel single-cell omics technologies, such as abundant omics exploration strategies, multiomics conjoint analysis mode, and deep learning network architecture, on the future research of breast cancer immune microenvironment.

Genetic Heterogeneity, Tumor Microenvironment and Immunotherapy in Triple-Negative Breast Cancer

“…Breast cancer development and progression are enabled and mediated not only by the proliferation of neoplastic cells, but also by numerous interactions with heterogeneous segments that create the surrounding tumor microenvironment. Such important factors are tumor-infiltrating lymphocytes, complex myeloid cells, lipid-associated macrophages, cancer-associated fibroblasts ( CAFs ), and other molecules that promote the growth and migration of tumor cells [ 99 ]. Tumor-infiltrating lymphocytes ( TIL ) are considered an important prognostic factor in various types of oncological diseases [ 100 , 101 , 102 , 103 , 104 ] including triple-negative breast cancer ( TNBC ) [ 105 , 106 ].…”

Integrated single-cell and bulk RNA sequencing analysis identifies the predictive signature for prognosis and neoadjuvant chemotherapy responses in breast cancer

“…These pathways have been implicated in several types of cancer and suggest that the differentially expressed genes identi ed in our study may play critical roles in regulating BC pathogenesis [29][30][31]. The nding that broblast, cancer cell, and cycling cell types have relatively high expression of NAC-related genes is particularly relevant as these cells are known to play important roles in BC pathogenesis [32][33][34][35].…”

Lipid Metabolism Heterogeneity and Crosstalk with Mitochondria Functions Drive Breast Cancer Progression and Drug Resistance

“…These TAM also express programmed-death ligand 1 (PD-L1) and PD-L2 and exert an anti-tumoral response. Considering the rich lipid sources of breast TME and the dependence on FA of tumor cells, lipid-associated macrophages may belong to the tissue-resident macrophage population that is reprogrammed by tumor cells [ 101 , 102 ]. On the contrary, another study showed that epidermal fatty acid-binding protein (E-FABP) is highly expressed in macrophages, particularly in a specific subset, promoting their antitumor activity.…”