Mapping immune cell dynamics and macrophage plasticity in breast cancer tumor microenvironment through single-cell analysis

Abstract

Breast cancer (BRCA) is a complex disease influenced by the tumor microenvironment, where interactions between immune cells and cancer cells play a crucial role in tumor progression and response to therapy. Understanding the intricacies of these interactions requires detailed analysis at the single-cell level, enabling the identification of specific immune cell subpopulations and their functional roles within the tumor milieu. This study comprehensively analyzed immune cell subpopulations and macrophage subtypes in BRCA using single-cell RNA sequencing technology and various computational tools. Initially, Sc-Type software accurately identified and annotated immune cell subpopulations, followed by CNV analysis using infercnv software, revealing significant CNV variations in epithelial cells. Subsequently, macrophages were re-clustered into 5 clusters, and their biological significance and functional features were assessed. CellChat analysis elucidated potential interactions between macrophage subtypes and BRCA cells, primarily through SPP1-CD44 and LGALS9-CD44 signaling networks. Additionally, CytoTRACE and Monocle were employed to analyze cellular plasticity and differentiation trajectories of macrophage subtypes. Furthermore, efferocytosis-related gene set scoring, transcription factor analysis, and risk score development were conducted, followed by immune infiltration and tumor mutation burden analysis, revealing increased immune infiltration and higher TMB levels in the high-risk group. These findings offer crucial insights into the interaction mechanisms of immune cells and macrophage subtypes within the BRCA tumor microenvironment, aiding in the understanding of tumor progression and therapeutic interventions.