These pharmacokinetic constraints highlight intrinsic limits of IgG-based PD-1/PD-L1 antibodies and motivate exploration of compact scaffolds and rationally designed small-molecule PD-1/PD-L1 inhibitors to mitigate size-limited diffusion (134), alongside nanomedicine-based localization to confine checkpoint effects to the tumor microenvironment (135). The gene discussed is PDCD1; the disease is neoplasm.