Fig. 4
Y332D inhibited tumor growth in murine tumor models, and the combination of Y332D and PD-1 blockade demonstrated synergistic antitumor effects. Tumor volume (TV) of tumor-bearing mice was measured every other day or every two days. Mice were euthanatized when TV exceeded 2500 mm3 or the study ended. a Model establishment and treatment schedule of H22 and EMT-6 tumor models. 8.7 mg/kg α-PD-1 were administrated every two days by intraperitoneal injection for four times. Equivalent mole hIgG (8.7 mg/kg), α-VEGF (8.7 mg/kg), α-TGF-β (6 mg/kg), Y332D (10 mg/kg) were administrated on alternate days by intraperitoneal injection for six times. b–d 5 × 105 H22 cells were inoculated subcutaneously in the right groin of BALB/c mice on day 0. Start of treatment on day 6. The representative tumors image, tumor growth curve, tumor weight of H22-bearing mice receiving α-PD-1 plus Y332D or controls treatment were shown. e The overall survival curves of H22-bearing mice receiving α-PD-1 plus Y332D or controls treatment were shown. f–h 5 × 105 EMT-6 cells were inoculated in the right mammary fat pad of BALB/c mice on day 0. Start of treatment on day 10. The representative tumors image, tumor growth curve and tumor weight of EMT-6-bearing mice receiving α-PD-1 plus Y332D or controls treatment were shown. i, j The representative image and tumor growth curve of EMT-6 tumors in the rechallenge assay were shown. *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001 denote the significant difference relative to Y332D or Y332D plus anti-PD-1 treatment. CR: complete regression. Bars, SDs; α-PD-1: anti-PD-1, α-TGF-β: anti-TGF-β, α-VEGF: anti-VEGF