Figure 10. GLI2 promotes NEXT by regulating TGF-beta-mediated non-classical Hedgehog signaling. (A–D) Down-regulation of GLI2 is accompanied by down-regulation of PD-L1, TGF-beta, IL6 and snail1. (E–H) Up-regulation of GLI2 is accompanied with increased expression of PD-L1, TGF-beta, and IL6. (I) Co-culture process. (J–L) Down-regulation of tumor-derived GLI2 decreases tumor-derived TGF-beta, PDL1 and IL6, likewise the NK-derived TIM-3 and PD1, while NK-derived IFN-gamma is increased. TGF-beta active protein powder restores the expression of tumor-derived PDL1 and IL6, and NK-derived TIM-3 and PD1. (M) Down-regulation of tumor-derived GIL2 leads increased secretion of NK-derived IFN-gamma, detected by Elisa.