Fig. 2: Spp1hi-TAMs in mouse prostate cancer are identified through scRNA-seq and demonstrate resistance to CSF1R blockade.
From: Evolution of myeloid-mediated immunotherapy resistance in prostate cancer
a, Schematic of 5′ scRNA-seq (10x Genomics) and CITE-seq (cellular indexing of transcriptomes and epitopes by sequencing) on immune (CD45+) and non-immune (CD45−) cells from mouse prostate cancer (MyC-CaP), subcutaneously engrafted on mice treated with degarelix or PBS. b, Cumulative MyC-CaP growth in mice, comparing degarelix-treated (red; n = 3) and PBS-treated (blue; n = 3) groups (P = 0.046). Symbols show mean ± s.e.m. c, UMAP plots showing the main cell types (left) and distinct myeloid subsets (right) in mouse prostate cancer. Prolif, proliferative; Inflamm, inflammatory; mono, monocytes. d, Heatmap comparing myeloid subset similarity scores between human (rows) and mouse (columns) prostate cancer. e, SPP1hi-TAM signature scores across myeloid cells (n = 6,397 cells) in mouse prostate cancer (P < 0.001 for comparisons of Spp1hi-TAM versus each subset). Enrichment scores were calculated using gene signatures in the patient dataset shown in Fig. 1. The red dashed line shows the median score for Spp1hi-TAMs for comparison. Boxes denote IQR; bars show 25% − 1.5 × IQR and 75% + 1.5 × IQR, with outliers exceeding 1.5 × IQR. f, Plot of differentially expressed genes (adjusted P-value < 0.05, |log2FC| > 0.5) (red), indicating enrichment or depletion in Spp1hi-TAMs versus other macrophages and monocytes. g, Schematic of anti-CSF1R or isotype-matched control antibody dosing in Spp1-EGFP mice after CRPC development, assessing myeloid composition 2 days after treatment. h,i, Quantification of cell number (h) and frequency (i) for macrophage subsets in CRPC mice treated with anti-CSF1R (n = 3) or isotype-matched control (n = 4) antibodies. Bars show mean + s.e.m. from 3 independent experiments; symbols represent individual mice. Significant changes were observed in CD163hi-TAM and CX3CR1hi-TAM populations (P = 0.02, P = 0.002 (h); P = 0.003, P = 0.03 (i), but not in Spp1hi-TAMs (P = 0.18, P = 0.30). Statistical significance was determined by two-sided unpaired Student’s t-tests (b,h,i), Kruskal–Wallis test with Dunn’s correction (e) and Wilcoxon test with Benjamini–Hochberg correction (f); *P < 0.05, **P < 0.01, ***P < 0.001; NS, not significant.
