A translational modelling study published in the British Journal of Cancer is challenging a foundational assumption in pembrolizumab dosing: that receptor occupancy of PD-1 on T cells directly predicts immune activation. The analysis reports that receptor occupancy may fail to align with downstream immune signaling responses, suggesting that clinicians and researchers may need to consider alternative pharmacodynamic markers. The work reframes how pharmacology and translational endpoints should be connected in immunotherapy trials, particularly when dose-ranging strategies rely on receptor saturation as a proxy for mechanism. For oncology programs designing immunotherapy studies, the implication is methodological—how pharmacodynamics are measured and interpreted may affect dose selection, patient stratification, and label-expansion evidence.