Fig. 4: Site-specific phenotypes of macrophages and functional reprogramming of SELENOP⁺ macrophages in the solid tumor microenvironment of metastatic HGSOC.
a The line plot showing the changes of relative fractions among macrophage clusters across the EAT, LAT and Met groups, p = 2.2 × 10−16, two-sided chi-squared test. Representative examples of ovarian tumor stained by multiplex immunohistochemistry, scale bar, 50 µm (b) and the quantification plots (c). For c, data are represented as means ± SD. Two-sided Kruskal–Wallis test, followed by Dunn’s post hoc test with adjustment. n = 20 samples from 11 HGSOC patients, including n = 5 EAT, n = 5 LAT, n = 5 Met. Ome, and n = 5 Met. Per, biological replicates. d Developmental trajectory of M05, M06 and M09 inferred by Monocle 2 analysis, color-coded by cluster (upper) and state (lower). Each dot represents a single cell. e Pathway enrichment analysis of the differential genes of cells in different state. Curve plots showing expression changes of function genes related to interferon signaling (f, left), SELENOP expression (f, right), HIF-1 signaling pathway (g, left), and SPP1 expression (g, right) along two cell fates. h Rank for regulons in SELENOP+ macrophages and SPP1+ macrophages based on regulon specificity score (RSS). i Heatmap showing transcription factors (TF) activity for SELENOP+ macrophages and SPP1+ macrophages. j Heatmap showing the RNA expression of TF along the pseudotime trajectory. k Western blot images (left) and quantification (right) of the levels of SELENOP proteins in THP-1 cells under control conditions or after treatment with 70 nM Se, 40 ng/mL IFNγ, or their combination. Se: Na2O3Se. l ELISA showing SELENOP level in the culture supernatants in (k). For k (right), l, data represent the mean ± SD. One-way ANOVA with Bonferroni post hoc test, n = 3, biological replicates. m Violin plots showing SELENOP expression of SELENOP+ macrophages across the EAT, LAT and Met groups, colored by mean expression. Box of violin plot represents median ± interquartile range, the whiskers extend up to the minimum and maximum values. p values are calculated by two-sided Wilcoxon tests, adjusted by the Benjamini–Hochberg procedure. For a, d–j, m, n = 17 scRNA-seq cohort solid site samples, biological replicates. Source data are provided as a Source Data file.
