This study suggests that sLRIG3, modulated by ADAM17 in GBM tumor cells, interacts with the CUB1 domain of NETO2 and plays a key role in attenuating the tilt towards an M2-dominant TAM population, thus remodelling the heterogeneous glioblastoma microenvironment, and suppressing GBM malignant growth. Here, ADAM17 is linked to glioblastoma.