T-cell surface glycoprotein CD96 (CD96)

T-cell surface glycoprotein CD96, also known as TACTILE, is a type I transmembrane protein and a member of the immunoglobulin superfamily primarily expressed on natural killer (NK) cells and T cells [4, 6]. It serves as a key component of the CD226/TIGIT/CD96 axis, where it competes with the activating receptor CD226 and the inhibitory receptor TIGIT for binding to their common ligand, CD155 (poliovirus receptor) [2, 12]. In the tumor microenvironment, CD96 typically functions as an inhibitory immune checkpoint that dampens the antitumor activity of NK and CD8+ T cells, thereby facilitating immune evasion by cancer cells [1, 9]. Beyond its role as a checkpoint, CD96 is highly expressed on leukemia stem cells in acute myeloid leukemia (AML), making it a valuable diagnostic marker and a specific target for chimeric antigen receptor (CAR) T-cell therapies [10, 14]. Therapeutic strategies targeting CD96, often in combination with PD-1 or TIGIT inhibitors, aim to restore and enhance the immune system's ability to eliminate solid tumors and hematological malignancies [3, 17].

Other names

TACTILET cell activation, increased late expressionCD96 antigen

Immune checkpoint inhibition (blocking CD96-CD155 interaction to enhance NK and T cell activity); Direct cell killing (via CAR-T targeting CD96-positive cells)