Fig. 6: Expressing GPR183 in primary human CD8+ T cells increases tumor infiltration and CAR T cell efficacy.
From: Engineering NK and T cells with metabolite-sensing receptors to target solid tumors
a, GPR183 cell surface expression in GPR183OE and control primary human CD8+ T cells. b–d, Transwell assay with flow cytometry-based quantification of control and GPR183OE primary T cell migration to 7α,25-OHC (b), MDA-MB-231 cell CM (c) and tumor and lung lysates (d); n = 6 technical replicates per group in b and n = 5 technical replicates per group in c and d. e–g, In vivo CAR T cell quantification and functional test. e, Experimental scheme. f, GPR183OE EpCAM-targeting CAR T cells accumulate in the tumor more than control CAR T cells, whereas their infiltration remains comparable in the lung and spleen. Representative flow cytometry plots (left) and bar plots show T cell number and relative abundance (right; n = 9 mice); m, mouse; h, human. g, IFNγ production and CD107a surface expression were quantified via flow cytometry in tumor-infiltrating CAR T cells isolated from nine mice at baseline and following ex vivo PMA/ionomycin stimulation. The data in f and g depict n = 4 mice treated with CAR T cells and n = 5 mice treated with GPR183OE EpCAM-targeting CAR T cells. h,i, In vivo antitumor efficacy of CAR T cells in NSG mice with EpCAM-overexpressing MDA-MB-231 xenografts. Tumor growth (h) and survival (i) curves of mice treated with control anti-EpCAM-CAR T cells (n = 6 mice) or GPR183OE anti-EpCAM-CAR T cells (n = 7 mice). Data are representative of two independent experiments for b–d. In vivo CAR T cell experiments were repeated with T cells generated from an independent donor (Extended Data Fig. 10c–e). Data are presented as the mean ± s.e.m. for b,d, f and g. In h, data are shown as the mean ± s.e.m. (left) and individual growth curves per mouse (right). Data analysis was performed using a one-way ANOVA with a Dunnett’s multiple comparisons test for b, two-way ANOVA with a Tukey’s multiple comparisons test for d, two-tailed unpaired Student’s t-test for c, f and g, two-way ANOVA with a Sidak correction for multiple hypothesis testing for h and log-rank test for i. Panel e created in BioRender; Jerby Lab https://biorender.com/c1gnk9g (2026).
