Figure 7 from GPR65 Inactivation in Tumor Cells Drives Antigen-Independent CAR T-cell Resistance via Macrophage Remodeling
Year: 2025
Type: other
Abstract: GPR65 KO–derived VEGFA fosters CAR T-cell therapy resistance. A, Chord diagram of cell–cell communication analysis performed using scRNA-seq data to quantify total interactions among m.CR tumors or GPR65 KO tumors, macrophages, and monocytes mediated by expressed ligands. Representative of scRNA-seq of tumor and TME performed at a tumor/TME ratio of 1:1 (CAR T cell–treated GPR65 KO tumor–bearing or m.CR tumor–bearing mice). B, Chord diagram showing GPR65 KO tumor–derived VEGFA ligand communication with host macrophages and monocytes. C, scRNA-seq analysis of VEGFA activity (left) and expression (right) in m.CR or GPR65 KO tumor cells isolated from mice 4 days after CAR T-cell treatment. Statistical significance was calculated using a two-tailed t test. D, Serum VEGFA concentrations in mice bearing no tumor, m.CR tumor, or GPR65 KO tumor 4 days after CAR T-cell treatment. Representative of two independent experiments. Significance was determined using one-way ANOVA with the Tukey post hoc test for multiple comparisons. E, Immunoblots showing VEGFA and actin protein levels in m.CR- or GPR65 KO–cultured tumor cell lysates. Representative of two experiments. D and F–I, Mice received 1 × 106 of the indicated tumor cells, followed by treatment with 10 × 106 CAR T cells 7 days later. F, Bioluminescence imaging showing tumor growth. Representative of two experiments, with n = 5 mice per group. G, Kaplan–Meier survival curves. Statistical significance was calculated using the log-rank (Mantel–Cox) test. Pooled from two experiments; n = 10 mice per group. H, Tumor and (I) macrophage cell numbers in the spleen and bone marrow of mice bearing the indicated tumor, 4 days after CAR T-cell treatment. Representative of two experiments, with n = 3–5 mice per group. Significance was determined using one-way ANOVA with the Tukey post hoc test for multiple comparisons. All error bars represent mean ± SEM. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001.
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4410047568