Tumor-associated stress antigen (TASA)

Tumor-associated stress antigens (TASAs) are a class of cell surface proteins, primarily comprising MHC class I polypeptide-related sequence A (MICA), MICB, and various UL16-binding proteins (ULBPs), that are upregulated in response to cellular stressors such as DNA damage, oxidative stress, and malignant transformation [1][2]. Under normal physiological conditions, these antigens are largely absent from the surface of healthy cells but become highly expressed on the surface of tumor cells, acting as "eat me" signals for the innate and adaptive immune systems [3]. They function as ligands for the NKG2D activating receptor found on Natural Killer (NK) cells, γδ T cells, and CD8+ αβ T cells, thereby facilitating the recognition and elimination of cancerous cells [4]. However, tumors often employ evasion strategies such as the proteolytic shedding of these antigens from the cell surface, which creates soluble decoys that desensitize immune cells and promote tumor progression [5]. Therapeutic strategies targeting TASAs include monoclonal antibodies designed to prevent shedding, bispecific engagers, and chimeric antigen receptor (CAR) T or NK cells engineered to recognize these stress-induced ligands [6].

Other names

Stress-induced ligandsNKG2D ligandsMHC class I-related chain A/BMICA/BUL16-binding proteinsULBPsStress-associated surface antigens

Binding and activation of the NKG2D (KLRK1) receptor on Natural Killer (NK) cells and CD8+ T cells to trigger cytolytic activity against stressed or malignant cells.