Figure 5 from GPR65 Inactivation in Tumor Cells Drives Antigen-Independent CAR T-cell Resistance via Macrophage Remodeling
Year: 2025
Type: other
Abstract: scRNA-seq characterization of mouse CR and GPR65 KO tumors. A, Uniform Manifold Approximation and Projection (UMAP) plot showing m.CR and GPR65 KO tumor populations from mice prior to CAR T-cell treatment (days 7 and 11) and after CAR T-cell therapy (day 11). B, Scatter plot highlighting key differentially expressed genes in CAR T cell–treated and untreated GPR65 KO vs. m.CR tumors. The x-axis represents log2 fold difference (log2FC) in gene expression comparing untreated GPR65 KO vs. m.CR tumors. The y-axis represents the log2 fold difference in gene expression comparing CAR T cell–treated GPR65 KO vs. m.CR tumors. The dotted line represents a log2 fold change cutoff at 0.25. Representative of scRNA-seq performed using five mice in each group. C, Bubble plots showing enrichment of statistically significant Hallmark pathways from MsigDB (v7.5.1) for day 7 (D7) untreated, day 11 untreated, and day 11 (D11) CAR T–cell treated GPR65 KO vs. m.CR tumors. Red represents normalized enrichment score (NES) in GPR65 KO tumors, and blue represents NES in m.CR tumors. The size of the bubble represents −log10 Benjamini–Hochberg-corrected P value, and black dots represent pathways that did not pass the statistical significance cutoff of P < 0.05. Representative of scRNA-seq performed using five mice in each group. D, Representative histograms and summary graphs showing expression of BCL2 in m.CR (red) or GPR65 KO (blue) tumors isolated from mice 4 days after CAR T-cell treatment. Representative of three experiments, with n = 5 mice per group. Significance was determined using an unpaired t test. MFI, mean fluorescence intensity. E, Immunoblots showing cMYC and actin protein levels in m.CR or GPR65 KO tumor cell lysates from culture (left) and their quantification (right). Representative of two experiments. All error bars represent mean ± SEM. *, P < 0.05; ***, P < 0.0001.
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4410047443