Characterizing the Tumor Microenvironment and Its Prognostic Impact in Breast Cancer

Abstract

The tumor microenvironment (TME) is crucial in cancer development and therapeutic response. Immunotherapy is increasingly recognized as a critical component of cancer treatment. While immunotherapies have shown efficacy in various cancers, including breast cancer, patient responses vary widely. Some patients receive significant benefits, while others experience minimal or no improvement. This disparity underscores the complexity and diversity of the immune system. In this study, we investigated the immune landscape and cell–cell communication within the TME of breast cancer through integrated analysis of bulk and single-cell RNA sequencing data. We established profiles of tumor immune infiltration that span across a broad spectrum of adaptive and innate immune cells. Our clustering analysis of immune infiltration identified three distinct patient groups: high T cell abundance, moderate infiltration, and low infiltration. Patients with low immune infiltration exhibited the poorest survival rates, while those in the moderate infiltration group showed better outcomes than those with high T cell abundance. Moreover, the high cell abundance group was associated with a greater tumor burden and higher rates of TP53 mutations, whereas the moderate infiltration group was characterized by a lower tumor burden and elevated PIK3CA mutations. Analysis of an independent single-cell RNA-seq breast cancer dataset confirmed the presence of similar infiltration patterns. Further investigation into ligand–receptor interactions within the TME unveiled significant variations in cell–cell communication patterns among these groups. Notably, we found that the signaling pathways SPP1 and EGF were exclusively active in the low immune infiltration group, suggesting their involvement in immune suppression. This work comprehensively characterizes the composition and dynamic interplay in the breast cancer TME. Our findings reveal associations between the extent of immune infiltration and clinical outcomes, providing valuable prognostic information for patient stratification. The unique mutations and signaling pathways associated with different patient groups offer insights into the mechanisms underlying diverse tumor immune infiltration and the formation of an immunosuppressive tumor microenvironment.