Granzyme B and Perforin-1 (GZMB/PRF1)

The granzyme B/perforin-mediated pathway is the primary mechanism by which effector cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells eliminate virus-infected or transformed tumor cells. Perforin is a pore-forming protein that facilitates the entry of granzymes, specifically the serine protease Granzyme B, into the cytoplasm of the target cell. Once inside, Granzyme B cleaves various substrates, including pro-caspase-3 and Bid, to trigger rapid DNA fragmentation and apoptosis. While not typically the direct binding target of small molecules, this pathway is the functional endpoint for many immunotherapy classes, including CAR-T cells, bispecific T-cell engagers (BiTEs), and immune checkpoint inhibitors. Dysregulation of this system is linked to immune evasion in cancer or, conversely, severe systemic inflammation and tissue damage in autoimmune or hyper-inflammatory conditions.

Other names

Granzyme BPerforin-1Fragmentin-2Cytotoxic T-lymphocyte-associated serine esterase 1Pore-forming proteinPFPH-PFP

Activation of effector T cells or NK cells leads to the release of perforin, which forms pores in the target cell membrane, allowing granzyme B to enter and initiate the caspase cascade, resulting in programmed cell death (apoptosis).