Tumor necrosis factor ligand superfamily member 6 (Fas ligand) (FasL)

Fas ligand (FasL), also known as CD178 or TNFSF6, is a type II transmembrane protein belonging to the tumor necrosis factor (TNF) superfamily [1]. It is a critical effector molecule expressed on the surface of activated natural killer (NK) cells and cytotoxic T lymphocytes. When FasL binds to its cognate receptor, Fas (CD95), it initiates the extrinsic apoptotic pathway in the target cell, a process essential for immune homeostasis and the elimination of virally infected or transformed cells [2]. In the context of ex vivo-generated NK cells, FasL expression is often enhanced or maintained during the expansion process to maximize the therapeutic potential of the cell product against malignancies [3]. While FasL is a potent anti-tumor tool, its systemic activation is limited by severe safety concerns, most notably acute hepatotoxicity due to high Fas expression in the liver [5]. Consequently, modern therapeutic approaches focus on localized delivery via cell therapies, such as CAR-NK cells, or the use of decoy receptors and modulated agonists to balance efficacy and safety [4, 6].

Other names

CD178TNFSF6CD95 ligandCD95-LApoptosis antigen ligandAPT1LG1

Fas ligand binds to the Fas receptor (CD95) on target cells, inducing receptor trimerization and the formation of the death-inducing signaling complex (DISC), which activates caspase-8 and leads to apoptotic cell death [1, 2].