Fig. 1: Adenosine uptake via ENT1 suppresses T cells.
From: Inhibition of ENT1 relieves intracellular adenosine-mediated T cell suppression in cancer
a, Resected tumor samples were frozen and adenosine levels determined by QMSI. Representative QMSI images of samples with low, medium and high adenosine levels (left to right). b, Mean concentrations of adenosine across all (n = 19) samples tested. Each symbol represents one sample (biological replicate); dotted bar indicates lower limit of quantification. Mean value shown; error bars, s.d. CRC, colorectal cancer; RCC, renal cell carcinoma; Endom., endometrial cancer; Mel., melanoma; HNSCC, head and neck squamous cell carcinoma. c, Expression of SLC29A (ENT) genes in activated human T cells during culture. Symbols represent mean values from three donors; error bars, s.d. P values from two-way ANOVA with Tukey’s multiple comparisons test. d, Flow cytometry analysis of surface ENT1 protein expression by CD8+ T cells at different time points of activation. Representative of three donors. e,f, Flow cytometry analysis of ENT1 expression on activated CD8+ T cells in relation to proliferation (e) and Ki-67 expression (f) after 72 h of culture. Representative of three donors. g, [3H]adenosine uptake assay using activated human T cells from three donors (biological replicates) in the presence of dilazep or DMSO; CPM, counts per minute. Mean value shown; error bars, s.d. P value from two-tailed paired t-test. h, Suppressive effect of 100 µM adenosine on CD8+ T cell proliferation and reversal with dilazep, an ENT1 inhibitor, combined with an A2AR antagonist. Representative of three donors. i–l, Suppressive effect of adenosine and restoration with dilazep and/or inupadenant on CD8+ T cell proliferation (i), T cell viability (j), TNF production (k) and IFNγ production (l). P values from two-way ANOVA with Tukey’s multiple comparisons test. Mean values from three donors; error bars, s.d.
