CD206+ macrophages dominate in breast adipose tissue and increase with obesity. A: Fibroglandular breast tissue exists in close proximity to adipose tissue that undergoes structural alterations during obesity, including increased fibrosis and infiltrates of macrophages, visualized as crown-like structures (CLSs). B: Schematic representation of macrophage polarization states and associated membrane molecule and enzymatic markers. C: Representative photomicrographs illustrating two spatially distinct compartments of macrophages in breast adipose tissue, CLSs that are composed predominantly of CD11c+ M1-biased macrophages, and interstitial macrophages, composed predominantly of CD206+ M2-biased macrophages, as determined by immunohistochemistry (IHC). D: The interstitium of breast adipose tissue contains more CD206+ versus CD11c+ macrophages regardless of obesity; however, CD206+ macrophage density is increased in obese versus lean women. E: Computational analysis of macrophage phenotype via CIBERSORT analysis of RNA transcripts corroborates IHC data with significant enrichment of M2-biased macrophages in obese versus lean breast tissue. D and E: Two-way analysis of variance was performed. Data are expressed as means ± SD (D and E). n = 26 sections, with 5 representative images per section (D); n = 26 (E). ***P < 0.001, ****P < 0.0001. Scale bars: 300 μm (A, main image); 100 μm (A, inset, and C). iNOS, inducible nitric oxide synthase.