Figure 1 from GPR65 Inactivation in Tumor Cells Drives Antigen-Independent CAR T-cell Resistance via Macrophage Remodeling
Year: 2025
Type: other
Abstract: B-ALL GPCR signaling predicts preclinical responses to CAR T-cell therapy. A and B, Mice received 1 × 106 m.PR or m.CR tumor cells (day 0) and 10 × 106 CAR T cells or PBS 7 days later. A,In vivo tumor bioluminescence imaging. Representative of three experiments, with n = 5 mice per group. B, Kaplan–Meier survival. Statistical significance was calculated using the log-rank (Mantel–Cox) test. Pooled from three experiments, n = 7 (m.PR); n = 15 (m.PR + CAR-T, m.CR, m.CR + CAR-T) mice per group. C, Surface expression of human CD19 on m.PR, m.CR, and m.PR relapsed tumor cells from in vitro culture or in vivo after relapse (day 24–35). Significance determined by one-way ANOVA with the Tukey post hoc test for multiple comparisons. MFI, mean fluorescence intensity. D and E, RNA-seq of in vitro cultured m.PR and m.CR tumor clones. n = 3 per group. D, Volcano plot highlighting top differentially expressed genes comparing m.CR and m.PR tumor clones. E, Functional enrichment analysis of upregulated differentially expressed genes in m.CR vs. m.PR tumors using REACTOME pathway gene sets (MsigDB v7.4). Pathways were filtered at Benjamini–Hochberg-corrected P value < 0.01. F, cAMP concentration in m.PR and m.CR tumor cells or media control, with n = 6 per group. Statistical significance was calculated using an unpaired t test. G, Immunoblots of pCREB and total CREB protein levels in m.PR and m.CR tumor cells. Representative of two experiments. All error bars represent mean ± SEM. ***, P < 0.001; ****, P < 0.0001.
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4410047835