A translational modelling study questions a core assumption behind pembrolizumab dosing: that saturating the PD-1 receptor on T cells predicts immune activation. Published in the British Journal of Cancer, the work reports that receptor occupancy fails to track with immune activation signals in the studied dosing context. The findings directly target the pharmacodynamic rationale used across the checkpoint inhibitor class, suggesting clinicians and modelers may need alternative biomarkers beyond PD-1 saturation to anticipate immunologic response. The paper also underscores the complexity of checkpoint pharmacology in vivo, where receptor engagement, T-cell trafficking, and downstream activation signals can diverge across time and tumor microenvironments. For drug developers, the result strengthens demand for more informative immune readouts when translating exposure–response relationships into dosing strategies.