T-cell surface antigen CD96 (CD96)

CD96, also known as Tactile, is a type I transmembrane glycoprotein belonging to the immunoglobulin superfamily [UniProt: P40200]. It is primarily expressed on the surface of Natural Killer (NK) cells and T cells, where it functions as an immune checkpoint receptor [PubMed: 24462216]. CD96 interacts with its primary ligand, CD155 (PVR), forming part of a complex regulatory axis alongside TIGIT and CD226 [PubMed: 24462216]. In the tumor microenvironment, CD96 typically delivers inhibitory signals that suppress NK cell activation and cytokine production, such as IFN-gamma [PubMed: 24462216]. Overexpression of CD96 is associated with immune exhaustion and has been linked to poor clinical outcomes in various malignancies, including hepatocellular carcinoma and acute myeloid leukemia [PubMed: 31953768]. Because of its role in dampening anti-tumor immunity, CD96 is a significant target for cancer immunotherapy [PubMed: 28468776]. Therapeutic strategies involve the use of monoclonal antibodies, such as GSK4074386, to block the CD96-CD155 interaction [ClinicalTrials.gov: NCT04381026]. These antagonists are often studied in combination with PD-1 or TIGIT inhibitors to achieve synergistic immune activation against solid tumors [PubMed: 28468776]. By neutralizing the inhibitory signal, these drugs aim to restore the cytotoxic potential of NK and T cells within the tumor [PubMed: 24462216].

Other names

TactileT cell-activated increased late expressionCD96 antigen

Antagonist; blocks the interaction between CD96 and its ligand CD155 (PVR) to prevent inhibitory signaling in NK and T cells.