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. 2023 Jan 31;83(7):1111–1127. doi: 10.1158/0008-5472.CAN-22-2553

Figure 7.

Figure 7. Antitumoral effect of Adora2b inhibition is CD8+ T-cell dependent. A, Schematic of KPC subcutaneous preclinical model to evaluate the role of Adora2b in PDAC tumor development. B, Mice lacking Adora2b (Adora2b−/−) presented delayed KPC subQ tumor growth compared with WT mice and (C) decreased tumor weight compared with WT mice. D, Tumor that developed in mice lacking Adora2b (Adora2b−/−) presented significantly increased CD8+ T cells (*, P < 0.05) and (E) significantly increased GZM staining per tumor volume compared with WT mice (**, P < 0.01; n = 14 fields/group). F, Chemical structure of PSB1115, Adora2b inhibitor, and (G) schematic of KPC subcutaneous preclinical model to evaluate the role of Adora2b in PDAC tumor development. H and I, Inhibition of Adora2b with PSB1115 reduces tumor growth rate only when injected in WT mice. The effect is lost when KPC cells are injected in CD8KO mice (*, P < 0.05; n = 8 mice per group). J, Trichrome staining to evaluate collagen abundance in control, Adora2b−/− and PSB1115-treated tumors. K, KPC tumors growing in Adora2b−/− had significantly reduced collagen compared with control tumors (*, P < 0.05); however, there was no difference in the percentage of collagen per field in tumors from PSB1115-treated mice (n = 12 fields analyzed per group). L, IHC for ⍺SMA to evaluate stromal changes in KPC tumors from Adora2b−/− and tumors from PSB1115-treated mice. M, The %⍺SMA+ staining was significantly decreased in KPC tumors grown in Adora2b−/− mice (****, P < 0.0001) and in tumors from PSB1115-treated mice (****, P < 0.0001); n = 15 sections per group.

Antitumoral effect of Adora2b inhibition is CD8+ T-cell dependent. A, Schematic of KPC subcutaneous preclinical model to evaluate the role of Adora2b in PDAC tumor development. B, Mice lacking Adora2b (Adora2b−/−) presented delayed KPC subQ tumor growth compared with WT mice and (C) decreased tumor weight compared with WT mice. D and E, Tumors that developed in mice lacking Adora2b (Adora2b−/−) presented significantly increased GZM staining per tumor volume compared with WT mice (n = 14 fields/group; D) and presented significantly increased CD8+ T cells (E). F and G, Chemical structure of PSB1115 (F), Adora2b inhibitor, and schematic of KPC subcutaneous preclinical model (G) to evaluate the role of Adora2b in PDAC tumor development. H and I, Inhibition of Adora2b with PSB1115 reduces tumor growth rate only when injected in WT mice. The effect is lost when KPC cells are injected in CD8KO mice (n = 8 mice per group). J, Trichrome staining to evaluate collagen abundance in control, Adora2b−/−, and PSB1115-treated tumors. K, KPC tumors growing in Adora2b−/− had significantly reduced collagen compared with control tumors; however, there was no difference in the percentage of collagen per field in tumors from PSB1115-treated mice (n = 12 fields analyzed per group). L, IHC for αSMA to evaluate stromal changes in KPC tumors from Adora2b−/− and tumors from PSB1115-treated mice. M, The percentage of αSMA+ staining was significantly decreased in KPC tumors grown in Adora2b−/− mice and in tumors from PSB1115-treated mice. n = 15 sections per group. *, P < 0.05; **, P < 0.01; ****, P < 0.0001; ns, nonsignificant.