GFRAL and cancer: In addition, GDF15 can also modulate the tumor microenvironment, innate immune surveillance, and response to immunetherapy.77 As the tissue distribution of GFRAL is limited to the hindbrain, direct effects of GDF15 on cancer or microenvironment immune cells may be mediated by yet unidentified GFRAL-independent signaling pathways.47 As such, consequences of direct inhibition of GDF15 on the tumor itself may be more difficult to predict.