Checkpoint inhibitors that target PD-1 or PD-L1 have had a profound effect in a variety of cancers, both as a single therapy and in combinations. We extend our previous QSP model-based analysis to test if PD-1:PD-L2 interactions are sufficient to explain the efficacy difference between the two drug classes observed in clinical meta-analyses. We also expand the analysis to include a virtual patient population (Vpop) to assess the effect of parameter variability on the model outcome.