Schematic of zoledronate-induced activation and regulation of NK cells. The current study by Nussbaumer et al²  suggests that zoledronate activates DC-like cells to produce mature IL-18 and IL-1β proteins, which stimulate NK-cell IFN-γ production by acting on IL-2–primed NK cells directly. Alternatively, zoledronate-activated DC-like cells can act on γδ T cells, which in turn costimulate IL-2–primed NK cells to enhance production of IFN-γ indirectly. Later, zoledronate-activated NK cells or γδ T cells may kill DC-like cells, thus terminating NK-cell IFN-γ production. In addition, a separate study by Maniar et al⁵  shows that zoledronate can activate γδ T cells to subsequently stimulate NK-cell cytotoxcity in the presence of hIgG1 or mAbs (red arrows). Professional illustration by Marie Dauenheimer.