Figure 6 from GPR65 Inactivation in Tumor Cells Drives Antigen-Independent CAR T-cell Resistance via Macrophage Remodeling
Year: 2025
Type: other
Abstract: GPR65 KO tumors reprogram macrophages with expansion and an M1 to M2 switch that confers CAR T resistance. A, scRNA-seq Uniform Manifold Approximation and Projection (UMAP) plot showing host immune cell populations from the TME of CAR T–treated mice bearing m.CR and GPR65 KO tumors. Representative of scRNA-seq of tumor and TME performed at a tumor/TME ratio of 1:1 (CAR T cell–treated GPR65 KO or m.CR tumor–bearing mice). B, Waterfall plot of the log2 ratio of indicated GPR65 KO vs. m.CR host TME populations. C, GSEA plot of IFNγ- and TNF-stimulated macrophage signatures (M1; top) and GSEA plot of IL4-stimulated macrophage signatures (M2; bottom) comparing macrophages in GPR65 KO tumor–engrafted and m.CR tumor–engrafted mice after CAR T treatment. P value is calculated using the Kolmogorov–Smirnov test. Representative of scRNA-seq of tumor, F4/80+ enriched macrophages, and nonmacrophage TME cells at a ratio of 1:3:2. D, GSEA plot of IFNγ- and TNF-stimulated macrophage signatures (M1; top) and of IL4-stimulated macrophage signatures (M2; bottom) comparing CD68+ macrophages from CD19+ relapse and h.CR patients’ bone marrow TME after CAR T treatment. P value is calculated using the Kolmogorov–Smirnov test. NES, normalized enrichment score. E, Bioluminescence imaging showing tumor growth in CAR T–treated mice depleted of macrophages (αCSF1R) or treated with isotype control. Representative of two experiments, with n = 5 mice per group. F, Kaplan–Meier survival curves pooled from two experiments, with n = 10 mice per group. Statistical significance was calculated using the log-rank (Mantel–Cox) test. Teff, T effector; cDC, Classical dendritic cells. All error bars represent mean ± SEM.
Language: English
Topic: Immune cells in cancer
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W4410047456