TNF and glioblastoma: Through spatial reprogramming, it elicits two synergistic effects: (1) the CD16-binding domain activates NK-cell ADCC, promoting release of PRF1 and GZMB and secretion of cytokines such as IFN-γ and tumor necrosis factor-α (TNF-α) 112; and (2) the IL-15 moiety enhances NK-cell persistence, expansion and effector function, thereby helping to counter GBM-associated immunosuppression 113.