Fig. 3: Adenosine inhibits pyrimidine synthesis in T cells following uptake by ENT1.
From: Inhibition of ENT1 relieves intracellular adenosine-mediated T cell suppression in cancer
a, CD8+ T cell proliferation in the presence of adenosine (50 µM) ± AdK inhibitor ABT-702 (300 nM). Representative example from three donors shown. b, Summary data from a. c, Dose–response curve of CD8+ T cell proliferation rescue effect of ABT-702 with a fixed dose of adenosine (50 µM). d, T cell proliferation in the presence of adenosine ± uridine or cytidine (all 30 µM). Representative example from five donors shown. e, Summary data from d. f, Dose–response curve of T cell proliferation rescue effect of uridine with a fixed dose of adenosine (30 µM). g, Pyrimidine metabolite levels in adenosine-treated relative to DMSO-treated activated human T cells. h, Summary of de novo pyrimidine synthesis pathway. i, Analysis of purine metabolites in T cells activated for 24 h in the presence of increasing concentrations of adenosine. j,k, Pyrimidine metabolite levels in activated human T cells treated with adenosine and/or dilazep (j) or additional reagents as indicated (k). Symbols represent each of the n = 3 (b,c,g,i–k) or n = 5 (e,f) donors; bars are group means; error bars, s.d. (b,e,g,i–k) with two-way ANOVA with Tukey’s multiple comparisons test (b,e) or mixed-effects model with Tukey’s multiple comparisons test (g,i–k).
