Fas cell surface death receptor (Fas) (FAS)

The Fas cell surface death receptor, also known as CD95 or TNFRSF6, is a critical mediator of the extrinsic apoptotic pathway and a member of the tumor necrosis factor receptor superfamily. Upon binding to its cognate ligand, Fas ligand (FasL/CD178), the receptor oligomerizes and recruits adapter proteins like FADD to form the death-inducing signaling complex (DISC), which subsequently activates the caspase cascade leading to programmed cell death. In the context of immunotherapy, Natural Killer (NK) cells—including untransduced (UTD) or engineered NK cells—utilize the Fas/FasL axis as a secondary killing mechanism to eliminate tumor cells that express the Fas receptor. While Fas is a potent target for inducing tumor regression, its therapeutic application has historically been limited by significant safety concerns, most notably life-threatening hepatotoxicity due to the high expression of Fas on healthy hepatocytes. Modern strategies focus on localized activation or the use of NK cell-based delivery to exploit this pathway while minimizing systemic side effects.

Other names

CD95Tumor necrosis factor receptor superfamily member 6TNFRSF6Apo-1 antigenApoptosis-mediating surface antigen FASAPT1FAS1

Agonism of the Fas receptor to induce the extrinsic apoptotic pathway via the formation of the death-inducing signaling complex (DISC) and activation of caspase-8.