Human endogenous retrovirus H long terminal repeat-associating protein 2 (HHLA2)

The human endogenous retrovirus H long terminal repeat-associating protein 2 (HHLA2, also B7-H7) is an immune checkpoint molecule and member of the B7 family. Unlike other B7 members, HHLA2 is present in humans but not mice. It is expressed primarily on the surface of monocytes/macrophages and occasionally on B cells after activation, as well as various epithelial cells in certain tissues. HHLA2 negatively regulates immune responses by inhibiting human T-cell proliferation and reducing cytokine production. In cancer, HHLA2 expression is often associated with an immunosuppressive microenvironment and poor prognosis, notably in hepatocellular carcinoma, triple-negative breast cancer, and other malignancies. Expression may also correlate with immune cell infiltration and is being explored as a novel target for immunotherapy, particularly in PD-L1-negative tumors. HHLA2 is under investigation as a prognostic biomarker and therapeutic target, with potential applications in boosting anti-tumor immunity

Other names

B7-H7HERV-H LTR-associating 2HHLA2 protein

Drugs targeting HHLA2 would likely act as immune checkpoint inhibitors to block its immunosuppressive signaling and boost anti-tumor T-cell activity