Figure 4 from GPR65 Inactivation in Tumor Cells Drives Antigen-Independent CAR T-cell Resistance via Macrophage Remodeling
Year: 2025
Type: other
Abstract: CAR T cells from mice with GPR65 KO tumors retain effector functions. A, Bubble plot with color showing fold change in expression of T-cell exhaustion and effector genes from CAR T cells isolated from mice with no tumor or m.CR or GPR65 KO tumors. n = 2–3 replicates per group. Log2FC, log2 fold change. B, Representative flow cytometry plots and summary graphs of PD-1 and Lag3 expression on CAR T cells from mice with no tumor or with m.CR or GPR65 KO tumors; n = 3–5 mice per group. Significance was determined by one-way ANOVA with the Tukey post hoc test for multiple comparisons. C, Percentage of CAR T cells expressing IFNγ, TNFα, IL-2, and GZMB in the spleen of CAR T–treated mice. Representative of three experiments, with n = 3–5 mice per group. Significance was determined by one-way ANOVA with the Tukey post hoc test for multiple comparisons. CAR T cells were activated for 7 days before transfer into tumor-bearing mice. The cells were isolated 4 days after transfer, restimulated with phorbol 12-myristate 13-acetate and ionomycin ex vivo, and stained intracellularly for cytokines. D, Schematic of the CAR T cell retransfer experiment. E and F, Mice received 1 × 106 m.CR tumor cells on day 0, followed by treatment with 2 × 106 fresh CAR T cells or CAR T cells isolated from m.CR or GPR65 KO tumor–engrafted mice 7 days later. E, Bioluminescence imaging showing tumor growth. Representative of two experiments, with n = 5 mice per group. F, Kaplan–Meier survival curves. Statistical significance was calculated using the log-rank (Mantel–Cox) test. Representative of two experiments, with n = 5 mice per group. All error bars represent mean ± SEM. *, P < 0.05; **, P < 0.01; ***, 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: W4410047509