Low affinity immunoglobulin gamma Fc region receptor III (CD16) (FcγRIII (CD16))

FcγRIII, commonly known as CD16, is a low-affinity receptor for the Fc portion of immunoglobulin G (IgG) that serves as a critical bridge between the adaptive and innate immune systems [1, 4, 14]. It is expressed on various effector immune cells, including natural killer (NK) cells, macrophages, monocytes, and neutrophils [1, 14]. The receptor exists in two distinct forms: FcγRIIIa (CD16a), an activating transmembrane protein, and FcγRIIIb (CD16b), a glycosylphosphatidylinositol (GPI)-anchored protein [14, 15]. Upon binding to antibody-opsonized targets, FcγRIIIa triggers potent effector functions such as antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis, leading to the destruction of tumor cells or pathogens [3, 10, 17]. In clinical oncology, FcγRIII is the primary mediator of the therapeutic effects of many monoclonal antibodies, such as rituximab and trastuzumab [3, 5, 13]. Genetic variations in the FCGR3A gene, particularly the V158F polymorphism, significantly impact the binding affinity of therapeutic antibodies and serve as important biomarkers for predicting clinical outcomes [4, 7, 13]. Beyond cancer, FcγRIII is involved in the pathogenesis of autoimmune diseases and the clearance of immune complexes [6, 14]. Therapeutic strategies often aim to enhance FcγRIII engagement to improve drug efficacy or modulate its activity to treat inflammatory conditions [6, 11]. However, overactivation can lead to safety concerns such as cytokine release syndrome or infusion-related reactions [11].

Other names

CD16Fc gamma receptor IIIFCGR3CD16aCD16bFCGR3AFCGR3BLow affinity immunoglobulin gamma Fc region receptor III-ALow affinity immunoglobulin gamma Fc region receptor III-B

Activation of antibody-dependent cellular cytotoxicity (ADCC), activation of antibody-dependent cellular phagocytosis (ADCP), and modulation of immune cell activation via ITAM-mediated signaling.