Fas ligand–Fas receptor complex (FasL–Fas)

The Fas ligand–Fas receptor complex (FasL–Fas) is a fundamental signaling unit of the extrinsic apoptotic pathway, playing a pivotal role in maintaining immune homeostasis and eliminating damaged or infected cells [1, 2]. Fas (CD95) is a transmembrane receptor belonging to the tumor necrosis factor receptor (TNFR) superfamily, which, upon binding to its cognate ligand FasL (CD178), undergoes trimerization and recruits the Fas-associated death domain (FADD) protein [1, 4]. This assembly forms the death-inducing signaling complex (DISC), which activates pro-caspase-8 and initiates a proteolytic cascade leading to cell death [2, 3]. In many cancers, tumor cells exploit this pathway by downregulating Fas expression to resist apoptosis or by upregulating FasL to induce apoptosis in attacking immune cells, thereby facilitating immune evasion [4]. Therapeutic interventions targeting this complex include Fas-agonists designed to trigger tumor cell death and decoy receptors like asunercept (APG101) that neutralize FasL to prevent its pathological signaling in diseases such as glioblastoma and myelodysplastic syndromes [5]. However, the clinical application of Fas-targeted therapies has been historically limited by severe systemic toxicities, most notably acute hepatotoxicity due to the high sensitivity of hepatocytes to Fas-mediated apoptosis [1, 4].

Other names

CD95/CD178 complexAPO-1/FasL complexTNFRSF6/TNFSF6 complexFas/FasL systemCD95/Fas ligand complex

Neutralization of Fas ligand to prevent Fas receptor activation or agonism of the Fas receptor to trigger the extrinsic apoptotic pathway.