CD160

CD160, also known as Cluster of Differentiation 160, is a glycosylphosphatidylinositol (GPI)-anchored protein encoded by the CD160 gene. It is alternatively termed BY55 or NK1, primarily expressed on natural killer (NK) cells, γδ T cells, and cytotoxic CD8+ T cells. Functionally, CD160 acts as a co-stimulatory or co-inhibitory receptor depending on cellular context, engaging ligands such as herpesvirus entry mediator (HVEM) to modulate immune synapse formation. Its interactions regulate cytotoxic activity, cytokine production, and cell survival, positioning it as a key player in immune tolerance and anti-pathogen responses. Dysregulation of CD160 has been implicated in chronic viral infections, autoimmune disorders, and tumor immune evasion.
The HVEM-CD160 axis intersects with pathways like the LIGHT/LTβR and BTLA-mediated signaling networks, influencing T-cell exhaustion and NK cell dysfunction. Clinically, CD160 overexpression correlates with poor prognosis in hematologic malignancies, while its deficiency exacerbates inflammatory diseases. Therapeutic strategies targeting CD160 are emerging, including antagonistic monoclonal antibodies to block immunosuppressive interactions in cancers and agonistic agents to enhance antiviral immunity. Preclinical studies demonstrate synergy with PD-1/PD-L1 checkpoint inhibitors, though no clinical-stage compounds have been reported. Structural studies of CD160-HVEM binding interfaces are guiding the design of bispecific antibodies and fusion proteins for precision immunotherapy.