Fas receptor (Tumor necrosis factor receptor superfamily member 6) (Fas)

Fas receptor (CD95) is a type I transmembrane protein and a prominent member of the tumor necrosis factor receptor (TNFR) superfamily that functions as a death receptor [1]. Upon ligation by Fas ligand (FasL/CD178), typically presented by effector immune cells such as Cytokine-Induced Killer (CIK) cells, the receptor trimerizes and recruits the Fas-associated death domain (FADD) protein [2, 3]. This assembly forms the death-inducing signaling complex (DISC), which activates pro-caspase 8 and 10, initiating a proteolytic cascade that culminates in the apoptosis of the tumor cell [3, 4]. In the context of CIK cell therapy—a heterogeneous population of CD3+CD56+ cells—the Fas/FasL pathway serves as a secondary cytotoxic mechanism alongside the perforin-granzyme pathway, allowing for non-MHC-restricted killing of malignant cells [2, 5]. Despite its potent anti-tumor potential, therapeutic targeting of Fas is complicated by its high expression in healthy hepatocytes, where systemic activation can lead to lethal liver failure [4]. Furthermore, many advanced tumors develop resistance by downregulating surface Fas expression or overexpressing decoy receptors like DcR3, necessitating strategies that combine Fas-pathway activation with agents that sensitize cells to apoptotic stimuli [4, 5]. Sources: [1] UniProt P25446; [2] Schmidt-Wolf et al. (2003) Gene Ther; [3] Peter & Krammer (2003) Cell Death Differ; [4] Wajant (2014) Exp Cell Res; [5] Sangiolo (2011) Expert Opin Biol Ther.

Other names

CD95APO-1TNFRSF6FAS1APT1Death receptor 2

Activation of the extrinsic apoptotic pathway through the formation of the death-inducing signaling complex (DISC) and subsequent caspase activation.