Fig. 1: DR-18 remodels the TME to promote effective tumor cell clearance.
From: IL-18: throwing off the shackles to boost anti-tumor immunity
In the TME, native IL-18 induces IFN-γ and IL-27 which act on macrophages to induce the decoy receptor IL-18BP in a negative feedback loop, neutralizing active IL-18. Engineered DR-18 evades IL-18BP but can still exert its function through IL-18R expressed on activated T cells and NK cells. NFAT activation, concomitant with NF-κB activation downstream of IL-18R signaling, curtails TOX expression, sustaining TCF1 expression and promoting effector T cell generation. DR-18 mitigates NK cell dysfunction in MHC class I-deficient tumors, leading to efficient cytolysis of malignant cells.
