Infiltration of CXCL9+ macrophages confers a favorable prognosis in breast cancer: Insights from an integrated single-cell RNA and bulk RNA sequencing study

Abstract

Background Breast cancer is the most common cancer among women and a leading contributor to disease-related mortality. While advancements in diagnostic techniques and the widespread dissemination of medical knowledge have improved outcomes, immunotherapy targeting the tumor microenvironment offers a promising approach to further reducing the disease burden. Methods We first explored cellular heterogeneity within breast cancer tumors using single-cell RNA sequencing and subsequently analyzed the association between the infiltration levels of various cell types and survival prognosis using a deconvolution algorithm combined with bulk RNA sequencing. Our analysis identified CXCL9 + macrophages as being associated with improved survival outcomes. Next, WGCNA was used to identify genes related to CXCL9 + macrophage infiltration, and a survival risk model was constructed based on these genes. Finally, experiments were conducted to validate the effects of CXCL9 + macrophages on breast cancer cells. Results We found that CXCL9 + macrophage primarily interacted with cytokines and activated T and NK cells through the CXCL9/10/11-CXCR3 axis. Increased infiltration, as observed in bulk RNA sequencing, was associated with improved patient survival. The risk model constructed based on CXCL9 + macrophage infiltration-related genes demonstrated strong efficacy in predicting patient survival outcomes. Finally, in vitro experiments confirmed that CXCL9 + macrophages inhibited the viability of breast cancer cells. Conclusion CXCL9 + macrophages could play a significant role in inhibiting breast cancer, and their infiltration into tumor tissues is associated with improved survival in breast cancer patients. Immunotherapy targeting CXCL9 + macrophages hold great potential as a therapeutic strategy.