Targeting nerve growth factor: an Achilles' heel for tumors?

A tumor's ability to attract innervation is a critical factor in tumor progression and immune escape, with the sympathetic nervous system playing a major role. Catecholamines released by sympathetic nerves activate adrenergic receptors on tumor cells, enhancing growth and resistance to therapies, while activation of adrenergic receptors on immune cells triggers immunosuppressive activity in the tumor microenvironment. Nerve growth factor (NGF) produced by tumor cells is a key driver of tumor innervation, making it a promising target for novel therapeutic strategies. In this commentary, we highlight a recent study by Yang et al, which examines NGF single-chain variable fragment (scFv)-secreting chimeric antigen receptor(CAR) T cells and the impact of NGF neutralization by CAR T cells on CAR T-cell function and the remodeling of the tumor microenvironment. This work shows that we may be able to exploit a tumor-derived survival factor as a vulnerability and a means to enhance antitumor immune activity.