ArticlePloS one2025
Infiltration of CXCL9+ macrophages confers a favorable prognosis in breast cancer: Insights from an integrated single-cell RNA and bulk RNA sequencing study.
Article in PloS one, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundBreast 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.
methodsWe 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.
resultsWe 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.
conclusionCXCL9 + 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.
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