Adenosine signaling through Adora2b on CD8+ T cells correlates with reduced survival and PDAC progression. A, TCGA analysis revealed that high expression of Adora2b human PDAC significantly correlates with worse prognosis (left). No differences were found in Adora2a (middle) or Adora1 (right). B,Adora2b expression in human PDAC positively correlates with Kras and Nt5E. C, Z score comparison of Adora2b-related genes shows a positive correlation with Kras and Nt5E, whereas a negative correlation was observed for Adora2a, Adora1, Adora3, Entpd1/CD39, and Pten. Z scores were downloaded from TCGA–PAAD cBioPortal. D, To analyze the distribution of immune cells in patients with high (n = 26) and low (n = 46) Adora2b expression in two groups, data analyzed with the Quantiseq algorithm were downloaded from The Cancer Immunome Database. Patients with high Adora2b expression presented a decreased abundance of B cells, CD8+ T cells, Tregs, NK cells, and M2 macrophages. Student t test was used to analyze significance. E, Similar results were observed when analyzing Immunome atlas data from patients with high (n = 44) and low (n = 103) expression levels of NT5E. Student t test was used to analyze significance. F, Patients with high Adora2b expression who have a lower abundance of activated CD8+ T cells present a worse prognosis. G, Analysis of genes expressed in activated CD8+ T cells confirmed lower overall expression of activated CD8+ T-cell gene expression in patients with high Adora2b expression. Z scores were extracted from The Cancer Immunome Database and TCGA–PAAD cBioPortal. **, P < 0.01; ***, P < 0.001; ****, P < 0.0001; ns, nonsignificant.