Fig. 7

Proposed model of NK cell function in BM upon adoptive cell therapy. Upper panels: NK cells activated with IL-15 infiltrate the BM and kill tumor cells with a faster kinetics than IL12/15/18 activated cells but their effect is more transient and is thus limited to a short time frame: upon initial activation of their anti-tumor function, IL-15 activated NK cells decrease their function and number starting from 48 h after transfer and their anti-tumor effect is no more evident after 7 days; on the other hand, IL-12/15/18 activated cells are poorly effective in the short time frame, this correlating with lower infiltration and slower activation of effector function than IL-15 activated cells. Nevertheless, they persist longer than IL-15 activated cells in BM and their anti-tumor effect becomes evident at 7 days after transfer. Lower panels: CXCR3 inhibition or genetic deletion increase activated IL-15 NK cell BM infiltration, thus improving and prolonging their anti-myeloma effect up to 7 days. Higher NK cell homing corresponds to improved engraftment in BM since transferred IL-15 NK cells persist up to 7 days. Conversely, IL-12/15/18 activated cells display long-term capacity to restrain tumor growth in vivo corresponding to better persistence in BM compared to IL-15 activated cells, but their BM infiltration and anti-tumor effect is not influenced by CXCR3