sPD-1V2 treatment suppresses tumor growth in ovarian cancer models that are PD-L2 dependent. A, ID8 PD-L1 CRSIPR tumors inoculated into PD-L1 KO mice. Tumor stained for PD-L1 and PD-L2 expression. Scale bar 50 μm. B, Subcutaneous ID8 PD-L1 CRSIPR tumor growth in C57BL/6 PD-L1 KO mice. Mice were treated with vehicle control, anti-mouse αPD-L1 blocking antibody, and sPD-1V2 (N = 8). C, Total tumor weight of ID8 PD-L1 CRISPR KO tumors at the time of termination. D, IHC staining of PD-L1 and PD-L2 in ID8 PD-L1 CRISPR KO tumors treated with vehicle control, anti-mouse αPD-L1 blocking antibody 10 mg/kg, and sPD-1V2 10 mg/kg. Scale bar 100 μm. E, ID8 ovarian tumor growth kinetics upon treatment with sPD-1V2 10 mg/kg, αPD-L1 antibody (10 mg/kg), αPD-L2 (10 mg/kg and 20 mg/kg), and the combination of αPD-L1 and αPD-L2 Abs (N = 5 for all experimental groups). F, Tumor growth kinetic of ID8 CRISPR PD-L1 and/or PD-L2 ovarian tumor treated with αPD-L1, αPD-L2 therapeutic antibodies, or sPD-1V2 to evaluate the tumor and/or stromal contribution of PD-L1, PD-L2 in ovarian tumor (N = 5 for all experimental groups). Statistical analysis used are one-way ANOVA for comparing between treatment groups and repeated ANOVA for changes over time. *, P < 0.05; **, P < 0.01; ***, P < 0.001.